TOPIC 13 - nerve and muscle Flashcards
what are the two nervous systems?
central and peripheral
what is the central nervous system?
- brain and spinal cord
- recieves, processes, interprets and stores information and sends messages destined for muscles, glands and organs
what is the peripheral nervous system?
- peripheral nerves
- transmits information to and from the CNS by way of sensory and motor nerves
what parts of the brain are in the CNS?
- forebrain (cerebrum, thalamus and hypothalamus)
- midbrain
- hindbrain (pons, medulla oblongata and cerebellum)
how many segments of the spinal cord are in the CNS?
31
what are the two divisions of the PNS?
- somatic
- autonomic (ANS)
what is the role of the somatic nervous system?
carries sensory information from sensory organs to the CNS and relays motor (movement) commands to muscle; controls voluntary movements
what is the autonomic nervous system divided into?
- sympathetic
- parasympathetic
- enteric and cardiac peluxes (intimately connected with parasympathetic)
what is the roles of the parasympathetic and sympathetic nervous systems?
sympathetic - fight or flight (speeds things up)
parasympathetic - rest and digest (calms things down
what are the main characteristics of neurones?
- high metabolic rates
- main component of brains ‘grey matter’
- dendrites for signal inputs
- axon for signal conduction
- synaptic terminals for signal output
what is a motor neurone?
- carries signals from CNS to outer parts of body
- have dendrites connected to the cell body, then axon then axon terminal
what is a interneuron?
- relay neurone
- connect various neurones within the brain and spinal cord
- dendrite not coming out of cell body but connected, cell body connected to axon then axon to axon terminals
what is a sensory neurone?
- carries signals from the outer parts of the body into the CNS
- dendrites connected to axon, cell body coming off of side of axon, axon terminals off of axon
what is a multipolar neurone?
a single long axon and many dendrites emerging from cell body (motor neurones)
what is a unipolar neurone?
found in sensory ganglia
what is a bipolar neruone?
found in sensory structures - eg retina
what is white matter and how does it stain?
- consists of axons carrying information to and from the brain
- will stain dark as has most myelin as mostly axons
what is grey matter and how does it stain?
- consists of cell bodies in sensory and motor nuclei
- stains pale as mostly cell bodies
what stain is used for myelin?
weigert’s stain
what are ganglia?
nodular masses of neuronal cell bodies (ganglion cells) and supporting neuroglia (satellite cells)
what are sensory ganglia?
cell bodies of sensory (afferent) neurons
what are autonomic ganglia?
cell bodies of motor (efferent) neurons from the autonomic nervous system
what does the epineurium do?
connective tissue layer that covers the whole nerve
what does the perinurium do?
covers a fasicle
what does the endoneurium do?
covers individual nerve axons
what is a fasicle?
a bundle of nerve fibres
what are neuroglia?
supporting cells for neurones
- regulate neurone metabolism and function
- repair and recovery from injury
- regulate blood brain barrier
- destroy pathogens and remove dead neurones
what types of neuroglia are in the CNS?
- astrocytes (most common)
- oligodendrocytes (most common in white matter
- microglia (less common)
- ependyma
what do astrocytes do?
structural - supportive framework
metabolic - provide neurone with nutrients
growth - promote neurone growth and synapse formation
blood brain barrier - restrict movement of substances from blood stream
potassium clearance - absorb K+ released from neurone at synapse
what do oligodendrocytes do?
myelinate axons (1 does up to 50)
what do microglia do?
immune defence - become phagocytic
what do ependyma do?
lining cells for the ventricles and central spinal canal, produce cerebral spinal fluid, have cilia on luminal side
what neuroglia are in the PNS?
schwann cells and satellite cells
what do satellite cells do?
surround nerve cell body and may aid in controlling chemical environment of neurons
what do schwann cells do?
form myelin sheath around large nerve fibres in the PNS and is also phagocytic
what is myelination?
- wrapping of axon in spiral of concentric layers of fatty myelinated membrane
- provides insulation to aid impulse transmission
what are nodes of ranvier?
gaps between adjacent cells
what do non-myelinated nerves have?
a supporting schwann cell - the axon is imbedded in a channel called the mesaxon (invaginations of the plasma membrane of the schwann cell)
what is a demylelinating disease?
a condition that results in damage to the myelin sheath —> nerve impulses slow/stop causing neurological problems
damage to the sheath can eventually lead to axonal degeneration
what is primary demylenating disease called?
leukodystrophic - myelin is abnormal and degenerates (usually genetic, some causes not known)
what is secondary demyelinating disease called?
myelinoclastic - healthy myelin is destroyed by a toxn, infectious agent, chemical or autoimmune substance
what is multiple sclerosis?
- common autoimmune demyelinating disease of the CNS
- loss of tolerance to self proteins —> inflammation and injury to myelin sheath and nerve fibres
what causes the sclerosis and scarring in MS?
- blood brain barrier is disrupted, allowing T cell entry to the brain
- T cells recognise myelin as foreign and attack it
- T cells release cytokines - promote degradation of myelin and blood brain barrier - B cells and macrophages can enter the brain
- B cells make antibodies to myelin (further degeneration)
- macrophages degrade myelin
what is located in the CNS, PNS and target tissue of sensory (1) and motor neurones (2)?
CNS - 1. axon terminals 2. cellbody and dendrites
PNS - 1. cell body and ganglion 2. axon
Target tissue - 1. sensory nerve endings 2. axon terminals
which autonomic nervous system has long preganglionic fibres?
parasympathetic
which autonomic nervous system has long and very branched postganglionic fibres?
sympathetic
where are the ganglia located in the parasympathetic and sympathetic nervous system?
parasympathetic - near or in target tissue
sympathetic - close to spinal cord
do both autonomic nervous systems have the same preganglionic transmitter?
yes - acetylcholine
do both autonomic nervous systems have the same postganglionic transmitter?
no
parasympathetic - acetylcholine
sympathetic - noradrenaline
how does erlanger-gasser classification work?
given a letter A B or C
what classification of nerve has the slowest conduction velocity?
C/IV - non myelinated - hot, pain, itch
what classification of nerve has the fastest conduction velocity?
A⍺/I - thick and v myelinated - propiroreceptors of skeletal muscle
what classification of nerve is for touch and pressure?
Abeta/II
what classification of nerve is for pain (fast) and cold?
Adelta/III
Going from A-C/ I-IV, what is the trend in diameter and velocity?
diameter and velocity decrease
how do you measure nerve conduction velocity?
place two electrodes either end of the nerve, measure distance between them and time for impulse to travel
how are sensory receptors classified by location?
exteroreceptors - external surface
interoreceptors - internal organs
prprioceptors - internal (position of muscles, tendons and joints)
how are sensory receptors classified by stimulus?
mechanoreceptors - touch, pressure, vibration stretch
thermoreceptors - hot, cold, temperature change
photoreceptors - light
chemoreceptors - chemicals
nociceptors - pain (usually chemicals)
sensory receptor - muscle spindles
found in skeletal muscles
respond to stretch
sensory receptor - free, endings uncapsulated
found in connective tissue, joints and skin
respond to pain, touch, light and pressure
sensory receptor - pacinian corpuscles
found in deep dermin, tendons, joints and genitalia, respond to vibration and deep pressure
sensory receptor - meissner’s/ krause’s bulbs
found in oral mucosa, lips, genitalia and fingertips
respond to touch, vibration and light pressure
sensory receptor - ruffini organs
found in deep dermis, ligaments and joint capsules
respond to stretch and deep pressure
outline the spinal cord reflex pathway
- sensory receptor detects stimulus
- sensory neurone transmits info to CNS
- integration centre - one or dome synapses in CNS
- motor neurone conducts efferent impulses to effector
- effector - muscle or gland that responds to impulses
what is the effect of negatively charged intracellular proteins in the nerve cell?
- they are large
- too big- cannot cross the cell membrane
- leave the cell and contribute to its negativity with respect to extracellular fluid as trapped inside
what does the sodium potassium ion pump do?
moves 3 Na+ ions out for every 2 K+ ions in.
= Thus inside of the cell gets more negative
what direction is the potassium ion gradient and what are its effects?
- K+ tends to leak out of the cell though selective channels down gradient as more potassium in cell than out due to conc gradient
- but…. cells large(-) charge inside = pulls K+ back in down electrochemical gradient due to the negativity in the cell
- eventually influxes become balances = K+ distribution equilibrium = -70mV
how is the equilibrium potential for an ion determined?
Nernst equation
used to calculate electrical potential of an ion of a particular charge across a membrane
whats the process of chemical transmission
- action potential reaches the axon terminal of the presynaptic cell.
- AP triggers calcium entry causing release of neurotransmitter chemical from the storage vesicles, which fuse with the synaptic membrane.
- Vesicles are “docked” and “primed” before action potential arrives – kept close to the terminal plasma membrane, so that release is as rapid as possible upon increase in calcium concentration.
- Upon calcium influx and concentration, the vesicle and plasma membranes merge
- the contents of the vesicles are released in to the synaptic cleft
how can we increase the probability of vesicle being released?
- by increasing calcium concentration) or decreased (i.e. by blocking depolarisation of the membrane and preventing calcium influx).
what is the sodium ion gradient and what effect does it have?
- the net inward diffusion gradient of Na+ slightly adds positivity of the cell
- Na + move into the cell due to the conc gradient
- Na+ move out of the cell due to the electrochemical gradient
- sodium ions both the concentration and electrical gradients operate in the same direction to cause inward flow of ions
- membrane is only slightly permeable to Na+ = effects on resting potential are small
- net effect of this is to bring the resting potential back up to about -65 mV
what is the value for the resting potential and how is it maintained?
- -65 to -70 mV
- electrical and chemical gradients acting on ions
- sodium potassium pump
what time of neurons have a resting potential value out of the normal range?
retinal neurones it is only -40 mV, in cortical pyramidal cells it is -75 mV.
-variation is due to differing levels of expression of ion channels in the membrane
what is the basis for the generation of an AP?
Ion flow across the membrane is the basis for signalling in neurones during action potentials- movement of ions contributes to AP
what is an AP?
means by which a neurone sends information down its axon, away from the cell body.
-The action potential (aka “spike” or “impulse“) is an explosion of electrical activity that is created by a depolarising current
describe the curve on the AP graph (the massive spike and then comes down)
membrane potential decreases and moves towards 0
becomes more positive until we get to +30mV: depolarisation
then charge becomes more negative and we reach -65mV: repolarzation
-then overshoot: membrane potential increases and so charge becomes more negative than -65mV : hyperpolerisation
describe the phases of an AP: phase 1 depolarisation
phase 1:
- Na+ channels open
- Na+ enters/diffuses into nerve cell (inward current)
- membrane potential rises
- resting membrane potential moves closer to zero and the cell becomes depolarised
- If negatively charged ions (e.g. Cl-) diffuse into a nerve cell across the membrane (outward current) the resting membrane potential moves further away from zero and the cell becomes hyperpolarised
- When the flow of ions stops, the potential rapidly returns to the resting level as the ions redistribute along and across the membrane according to their concentration/potential differences and permeabilities (i.e. negative feedback effect to maintain the status quo).
how does Ca influx lead to release of transmitter in an electrical synapse
- Action potential arrives at synaptic terminal causing depolarization.
- Voltage-gated Ca2+ channels are opened by depolarization and Ca2+ ions rush into the terminal.
- With rise in [Ca2+]I vesicles move to active zone, undergo fusion with membrane and release contents.
- membrane of the synaptic vesicle fuses to the presynaptic membrane at the active zone (docking), allowing the contents of the vesicle to spill out into the synaptic cleft
- Ca2+ enters the axon terminal directly at the active zone, precisely where vesicles are primed and ready for exocytosis, ensuring a rapid release of neurotransmitter.
- Fused vesicle membrane is taken back into the cell by endocytosis.
describe the phases of an AP: phase 3 repolarisation
- Na+ channels close so less sodium into cell as electrochemical force driving their movement has diminished due to overshoot
- voltage gated K+ channels open as potential difference for K+ is now far from equilibrium and K+ ions flow out of cell -increased potassium conductance-causing a rapid repolarisation back towards the resting membrane potential.
- membrane potential reverses
describe the phases of an AP: phase 3 hyperpolarisation
- When the resting membrane potential is reached the K+ channels are still open K+ ions continue to flow out of cell while Na+ channels closed (so K+ movement not opposed by this)
- membrane potential overshoots past the normal resting level -falls below resting level-(hyperpolarisation) for a brief period before the normal resting potential is restored
- During this brief period (refractory period) another action potential cannot be generated, so APs cannot summate and can only travel one way along the axon
what is required for ion influx to occur?
the threshold has to be reached and so the Na+ and K+ channels open
what determines the activation and inactivation of gates?
groups of charged amino acid residues at critical points of the ion channel structure that form the ion pore
whats gates are open and closed during resting state?
all voltage gated Na+ and K+ channels closed
NB- K+ channels are different to the ones that allow K+ to pass through membrane at rest
what gates are open and closed during the depolarising phase?
- voltage gated Na+ channel fast activation gates open (at about -40mV)
- Na+ can now enter cell, so inside becomes more positive – it depolarises
- this opens more activation gates = accelerating the flow of ions
what gates are open and closed during the overshoot phase
- inactivation gates of Na+ channels start to close and activation gates of K+ channels begin to open and K+ ions begin to exit the cell
- electrostatic force attracting Na+ into the cell becomes neutralised Na+ no longer able to enter cell, so no further depolarisation occurs as anterior of the cell becomes more negative
what gates are open and closed during repolarisation phase
inactivation gates of Na+ (fully closed) channels closed and K+ channels open= k+ rapidly leave the cell so membrane returns towards resting potetial
-K+ can now leave cell, so inside becomes more negative – it repolarises
what gates open and close during undershoot pahse/after potential?
K+ channels still remain open, Na+ channels closed
-K+ continue to leave cell, so inside becomes even more negative than the resting potential – it hyperpolarises
what gate are open and closed during the resting state
all voltage gated Na+ and K+ channels closed
-No movement of ions across membrane, so resting potential restored
(-65mV)
Whats the all or nothing principle?
- A neurone either fires or it does not, regardless of signal size – “all-or-nothing”
- A stimulus (e.g. injection of current) insufficient to raise the membrane potential to the threshold potential will never induce an AP
what impact does a stimulus have its its above threshold?
Further increase above threshold -> higher AP frequency not larger AP amplitude
what is a threshold?
All excitable cells have a threshold membrane potential
-Membrane has to be depolarised beyond threshold for an AP to be generated
what is the absolute refractory period?
During the absolute refractory period no further action potentials can be elicited no matter how much you stimulate it
This refractory period means that an action potential can only travel along the axon from cell body to axon terminal, not in the opposite direction. It cannot reverberate (i.e. go backwards towards its point of origin – normally the point where the axon joins the nerve cell body- cant get depolariation upstream).
what happens during the relative refractory period?
a larger stimulus can result in action potential
explain the action of AP along a non-myelinated axon
- Na+ influx deplorises area in front of it and triggers voltage gated Na+ channels to open
- causes AP in the next membrane section
- membrane behind impulse is refractory
- impulse can only go forward along the axon
explain the action of AP along a myelinated axon
- nodes of Ranvier are the only areas where current can pass through membrane
- nodes are only areas where membrane can depolarise
- excess of positive charge causes impulse travels in ‘jumps’ from one node to another and from there out into the extracellular space, causing depolarisation and an AP at the next Node- not slow flow
- AP jumps along the axon from Node to Node (salutatory conduction) – a much quicker means of conduction than in the non-myelinated fibre.
what are at the end of sensory neurones?
sensory receptors
what are sensory receptors
tuned’ to specific signals or sensory modalities, i.e., different forms of energy (light, vibration, chemicals, etc.)
what is sensory transduction?
conversion of environmental or internal signals into electrochemical energy.
what does detection of stimulus by reeptor cause?
- receptor potential
what is a receptor potential
- Graded electronic response (not action potential)
- Causes action potential
- receptor potential can build up to from AP
- Specific signals – rate and pattern of action potential firing – decoded in CNS
what does the magnitude of a receptor potential depend on
strength of stimulus
- If the receptor potential is large enough and the neurone reaches threshold, an action potential occurs
- An even stronger stimulus results in an increased number of action potentials
what 2 sensory receptors in muscles respond to stretch
proprioceptors and mechanoreceptors
where is the muscle spindle located and how is it stimulated?
within the muscle and stimulated when the muscle is passively stretched.
where is the golgi tendon organ located and what does it respond to?
is located in the tendon and responds to tension (it is stimulated when associated muscle contracts or is stretched).
describe the muscle spindle and its role
bundle of modified skeletal muscle fibres (intrafusal fibres) enclosed in connective tissue capsule. Intrafusal fibres detect stretch and initiate reflex which causes the muscle to contract to reduce the danger of over stretching
describe the golgi tendon organ and its role
small bundles of tendon (collagen) fibres enclosed in a layered capsule with the terminal branches of a large diameter (mechanoreceptive Ib) , ib aafernt ,afferent fibre intertwined with collagen bundles. Stimulated when the associated muscle contracts or is stretched. Sets up reflex causing muscle to relax and removing stimulation. Senses changes in tension/force.
how does the muscle spindle work?
- When a muscle is stretched passively the spindle is activated
- increasing firing of AP and so initiates a reflex causing mulches to contract.
- When the muscle contracts and shortens it is switched off.
- Protects muscle being overstretched
what is the knee-jerk reflex pathway an example of and how does it work
muscle spindle pathway
- This is a monosynaptic stretch reflex:
- Stretching of the muscle stretches the spindle -Striking the patellar ligament with a reflex hammer just below the patella stretches the intrafusal fibres of the muscle spindle in the quadriceps muscle activates them resulting in increased discharge of the sensory nerves.
- the stimulus produces impulses in sensory afferent fibres (type Ia) This results in increased firing of the motor neurone and the muscle contracts.
- No spinal interneurone is involved in this case- only at the level of L4 in the spinal chord, independent of higher centers
- alpha-motoneurone conducts an efferent impulse back to the quadriceps muscle, triggering contraction. This contraction, coordinated with the relaxation of the antagonistic flexor hamstring muscle causes the leg to kick-involves inhibitory interneurone in relaxation of the antagonistic hamstring muscle
- The effect is to dampen the stretch of the muscle.
- Specific for the muscle stretched
in what state is GTO active?
passive stretch and active contraction
what is the main function of the GTO
tension detector that protects muscle against excess load
Function to protect the muscle and connective tissue from injury
how is the GTO stimulated?
excessive tension during muscle contraction or passive stretch
what does the GTO do?
Causes a reflex inhibition of the muscle ……relaxation before tendon tension becomes high enough to cause damage
Helps prevent excessive muscle contraction or passive muscle stretch
what are the steps to GTO effect
- Sends AP down sensory afferent fiber
- Activates inhibitory interneurone
- Inhibits alpha motor neurone that supplies muscle
- Reduces no AP in neurone
- Muscle relaxes
- Excessive tension relived
- Same time activate sensory efferent neurons activate effterent tendon neurone causing it to contract as activates antagonistic muscle
what are the 2 types of synaptic junctions
- electrical synapses: direct passage of current via ions flowing through gap junctions from one cell to another
- Chemical synapses: release of vesicles containing chemical transmitter which has an effect on receptors on a pro-synaptic target cell.
where are electrical synapses found?
More common in invertebrate nervous systems, but do occur in human brain and may be involved in epileptiform activity.
what are gap junctions made of
Formed by interlocking connexon channels of adjacent neurones. Connexons comprise connexin proteins.
where are gap junctions found
present at points of contact between neurones with no synaptic cleft, only a very narrow gap between their membranes – ions and therefore current flow can pass directly from one cell to the next – resulting in direct, very fast electrical transmission between neurones.
what direction do ions flow in gap junctions
Current flow is usually unidirectional in electrical (rectifying) synapses in the mammalian CNS, but can be bidirectional (non-rectifying) in invertebrates
what is a chemical synapse and what does it do
Interface for chemical communication between neurones.
Release of transmitter from synaptic vesicles on arrival of an action potential in the terminal ‘bouton’ of neuronal axon
whats the process of chemical transmission
- action potential reaches the axon terminal of the presynaptic cell.
- AP triggers calcium entry causing release of neurotransmitter chemical from the storage vesicles, which fuse with the synaptic membrane.
- Vesicles are “docked” and “primed” before action potential arrives – kept close to the terminal plasma membrane, so that release is as rapid as possible upon increase in calcium concentration.
- Upon calcium influx and concentration, the vesicle and plasma membranes merge
- the contents of the vesicles are released in to the synaptic cleft.
- Probability of release – a vesicle either will or won’t be released. The probability of release can be increased
what is a NT
A substance that is released at a synapse by one neurone that affects another cell, either neuron or effector organ, in a specific manner and have a physiological action on specific receptors on a target cell
what is neuromodulator
a substance that is released and modifies the action of a transmitter, but doesn’t have a direct action itself
what is neuroactive substance
– a neutral term if a substance is known to have an effect in the CNS but its precise action is not known
what is the most common NT
Acetylcholine
name some amine NT
Dopamine (DA) Noradrenaline (Norepinephrine)(NA) Adrenaline (Epinephrine) Histamine Serotonin (5-hydroxytryptamine 5-HT)
name some AA NTs
Gamma-aminobutyric acid (GABA-inhibitory)
Glutamate (Glu)-ecitory
Glycine (Gly)-inhibiotry
name some peptide NTs
Dynorphin Enkephalins Neuropeptide Y (NPY) Calcitonin gene-related peptide (CGRP) Somatostatin Galanin Substance P (SP) Thyrotropin-releasing hormone (TRH) Vasoactive intestinal polypeptide (VIP)
how does Ca influx lead to release of transmitter
- Action potential arrives at synaptic terminal causing depolarization.
- Voltage-gated Ca2+ channels are opened by depolarization and Ca2+ ions rush into the terminal.
- Entry calcium into terminal= vesicles move to active zone terminal= fuse with membrane and release contents into synapse
- Taken into via endocytosis
what are active zones?
specialised areas on presynaptic membrane that guide the vesicles towards the membrane
what does binding of a NT to the receptor cause?
conformational change in the receptor proteins, and the protein functions differently.
what are the 2 NT receptors?
- Ionotropic receptor
- Metabotropic receptors
what is a ionotropic receptor?
- cluster of similar subunits forming ion channels, that depolarise or hyper-polarise the postsynaptic cell (fast responses): depending on the kind of postsynaptic cell different affect
- when ligand binds: conformational change that briefly opens the pore and ions pass through to cause a rapid change in the resting potential of the underlying cytoplasm
- mostly 4 or 5 similar protein subunits arranged around a central pore that is normally closed to ion movements
what is a metaotropic receptor?
is a 7-transmembrane molecule coupled to intracellular proteins that transduce a signal to cell interior (slow responses)
- long protein molecules, mostly crossing the cell membrane 7 times
- no ion pore
- ligand binds: conformational change in the molecule that causes the intracellular part to interact with a G-protein that then sets off a chain of intracellular events
what happens when glutamate or acetlycholine binds to receptor?
- influx Na+ ions giving rise to an excitatory post-synaptic potential (EPSP)- can result in formation of AP in postsynaptic cell
- EPSPs depolarise cell brining it closer to threshold potential and may initiate an AP
what happens when inhibitory NT GABA and glycine binds to inhibitory transmitter receptors?
-associated with cl channels
efflux of K+ or influx of Cl- causing a net outward current. This results in an inhibitory postsynaptic potential (IPSP) bringing the postsynaptic cell further away from the threshold for firing action potentials – i.e. hyperpolarising it as it beings negative charge in - harder to fire AP
if more transmitter is released what effect does this cause?
more ion channels open (greater conductance), the greater the current flow and so the greater the EPSP or IPSP, i.e. summation of individual channel postsynaptic potentials. One action potential leading to release of transmitter results in only an EPSP or IPSP. Many action potentials (e.g. From multiple synapses on same postsynaptic neurone) cause the threshold for firing to be reached and so an action potential is initiated in the postsynaptic neurone
give 5 features of the excitory post synaptic potentials?
No threshold
Decrease resting membrane potential
i.e. closer to threshold for depolarization
Graded in magnitude
No refractory period
Can summate (ie. add up)inhibitory post synaptic potentials?
No threshold
Hyperpolarize post synaptic membrane
Increase membrane potential
i.e. moving it further from threshold for depolarization- harder to fire AP= silence cell
No refractory period
Can summatewhat is a motor unit?
-consists of the motor nerve and all the muscle fibres innervated by that nerve.
how do muscle fibers in a motor unit contract?
all the muscle fibers in a motor unit contract together when the motor nerve fires
what does the size of motor unit depend on?
function of muscle
what is 1:1 transmission?
A chemical transmission which is designed so that every presynaptic action potential results in a postsynaptic one
corresponding muscle AP for AP being transmitted down the nerve
does neuromuscular transmission have a time delay ?
yes
inherent delay 0.5-1ms
unidirectional
do drugs effect the neuromuscular transmission?
yes and other factors due to various steps in transmission
what is the neuromuscular junction and what are the specialised regions of prejunctional and postjunctional?
a specialised region prejunctional: large SA- for NT to be released lots of mitochondria lots of vesicles
postjunctional:
indentations= increase SA exposed to motor end plate
where is the neuromuscular junction?
The synapse between motor neurons and skeletal muscle fibres
what does the neuromuscular junction do?
Bridges” the motor nerves and skeletal muscle fibres.- not in direct contact= have synaptic cleft
the highly specialised point of contact between the motor nerve cell carrying information from the CNS to the muscle fibre cells
what are post junctional folds on the NMJ and why are they useful?
where NT receptors are concentrated
- effiecent way to signal across the gap keeps all active components of signalling process together
what is the process of the NMJ sending out a signal?
- Motor nerve cell bodies sited in the ventral horn of the spinal cord send out axons via ventral roots to innervate the appropriate muscles.
- These axons are myelinated as they pass through the CNS and into the peripheral nerves but divide to supply thin unmyelinated fibres, which can each innervate several individual muscle fibre cells.
- Each axon terminates in a swollen end, or bouton – this is the point of contact with the muscle cell and is where the neurotransmission actually occurs.
- Action potential propagate down this nerve, from the CNS, travel along the unmyelinated axons, and trigger neurotransmitter release from the swollen terminals onto the muscle cells.
describe the steps in NMJ transmission
- arrival of AP at presynaptic cell
- causes depolarisation of the terminal membrane/bouton
- opening of voltage gated clacium channels
- influx of calcium into synaptoc bouton
how do we ensure that ONLY vesicle release and not other cellular cascades are trigged by calcium increase?
microdomains serve to keep the calcium increase localised to area around vesicles only
describe the process of NMJ chemical transmission
- fusion of vesicles to synaptic membrane
- exocytosis - release of Ach into synapse
- binding of Ach to nicotinic receptors on muscle cell membrane
- receptor activation
- Na+ enters the cell
- membrane depolarisation
what is the structure of an nAChR?
- each receptor formed from 5 units
- each subunit = 4 transmembrane spanning segments
- 2 alpha subunits = Ach binding sites
when must the ACh bind to the alpha binding sites of nAChR
before receptor activation
what do the different subunits in the nAChR effect ?
Different subunit types so different types of nAChR depending on composition – affects pharmacological profile.
in MEPPs what does 1 quantum of NTs equal
contents of 1 synaptic vesicle
how many receptors does ACh activate
1000-2000 receptors
what is MEPPs
miniature end plate potentials
= depolarisation produced by single quantum of Ach
-Causes local depolarisation of around 0.5mV
what triggers MEPPs to be released
Random occurrence without action potential or calcium influx = small MEPPs = voltage they produce too smlal
smallest measurable event in transmission – i.e. don’t get parts of quanta released, either 1 quantum or multiples of 1
are MEPPs additive?
yes
Many MEPP’s togetheras lots of vesicles relased at once (i.e. when action potential causes release of many vesicles) forms EPP – generates action potential.
what happens if EPPs cause membrane to reach threshold?
voltage gated ion channels in the postsynaptic membrane open > influx of Na+ > action potential > leading to muscle contraction
how is ACh inactivated?
- AP depolarises synaptic knob
- Ca2+ enter cytoplasm and after brief delay ACh is released through exocytosis of synaptic vesicles
- ACh briefly binds to postsynaptic sodium receptors producing graded depolarization
- Ach dissociation from receptor hydrolysed by the enzyme acetylcholinesterase (AChE)
- ACh> Acetate + Choline by AChE
- synaptic knob reabsorbs choline from terminal and uses it to synthesise new molecules of ACh
what is between the post and pre synaptic neurones in a synaptic cleft?
basal lamina (support within synaptic cleft) and enzyme for ACh breakdown (acetylcholinesterase (AChE) in cleft, attached to basal laminae.
how does ACh work
1-AP reach axon terminal
2- inside membrane hyperpolisated compared outside - calcium influx into terminal from AP= depolarisation = positive in the membrane
3- depolarisation = opens voltage gated calcium channels
4- allow influx of calcium
5- Ca indices fusion of vesicles with terminal membrane
6- Ach released into synaptic cleft
7- Ach binds to nicotinic receptor
8- opens channel pore in nicotinic receptor
9- allows movement of Na in and k out = depolarisation
outline the life cycle of a synaptic vesicle
1) Acetate reacts with co-enzyme A forms acetyl-CoA which reacts with choline to form ACh.
2) ACh concentrated within vesicle coupled to counter transport of H+.- so choline transported in and H+ out. Requires H+ gradient which is an active process.
3) Reserve vesicles anchored near active zone by synapsin that tethers them to actin filaments
(4) Docking of vesicles. v-Snare protein on vesicle binds to t-Snare on membrane at active zone at presynaptic membrane.
5) Ca2+ channels activated by action potential - Ca2+ influx.
6) Raised Ca2+ triggers membrane fusion and ACh release (exocytosis)- triggers fusion of vesicle with presynaptic membrane
(7) Release of vesicles from reserve with actin.
8) ACh diffuses across cleft and binds to nicotinic receptor, opening channel.
9) ACh broken down by AChE in basal lamina to choline and acetate by acetylcholinesterase, bound mainly to basal lamina.
10) Choline taken up into nerve terminal by cotransport with Na+.
11)1Vesicles become part of membrane, endocytosis, clathrin coated and internalised. Fuses with endosome, new vesicles formed from budding- new cycle.
12) portions of membrane that bud off become clahtriin coated and form endosome= form vesicles
13)
how is acetlycholine synthesised?
The precursor, choline derived from the diet is taken up by the neurone by a sodium dependent choline transporter. Acetyl coenzyme A, is synthesised from glucose and/or fatty acids. Synthesis of ACh occurs in the cytoplasm due to the presence of choline acetyl-transferase enzyme in cholinergic neurones.
whats the Method of concentrating ACh into vesicles
energy dependent process via specific sodium dependent ACh transporter - co-transport – H+ down gradient (out of vesicle) – exchanged for molecule of ACh – transported into vesicle.
wht are the 3 diff pools of vesicle present?
- Ready releasable pool – undergo exocytosis in response to a single action potential as they have been primed by docking at the active zone.
- Recycled synaptic vesicle pool.
- Reserve pool – ensures that neurotransmitter is available even for the highest physiological demands.
what kind of drug is curarine and what are its effects?
- paralyses the skeletal muscle
- doesn’t kill you
- non depolarising agent
what kind of drug is tubocurarine
non depolarising competitive nAChR antagonist
-act by competitively blocking the binding of ACh to its receptors-it is a form of neuromuscular blocker that does not depolarize the motor end plate.
what is the mechanism by which tubocurarine works
- in small doses Competes with Ach for nicotinic receptor binding sites - muscle paralysis occurs gradually.- blocks action of Ach
- At higher doses they can block pre-junctional Na+ channels thereby decreasing ACh release.
how long do the effects of tubocurarine last?
30 mins
what can reverse the effects of AChE inhibitors
- Neostigmine
- Hydrolysed by circulating esterases
whats the therapeutic use of tubocurarine
- historically paralytic surgery
- neuromuscular block is used adjunctively to anesthesia to produce paralysis
- help paralyze the vocal cords, and permit intubation of the trachea, and secondly to optimize the surgical field by inhibiting spontaneous ventilation, and causing relaxation of skeletal muscle
what are the adverse effects of tubocurarine
decrease BP/hypotension (explained by its effect of increasing histamine release, a vasodilator or potentially via ganglion blockade)
bronchospasm
what kind of drug is succinylcholine
Depolarising nAChR agonist
by what mechanism does succinylcholine
Persistent depolarization of the neuromuscular junction.
acts in 2 parts
Phase I: Membrane depolarized by opening AChR channels = brief period of muscle fasciculation (twitching) as nictonitic receptors activated- activation and excitation
Phase II: End plate eventually repolarizes, but because Succinylcholine is not metabolised and is bound as rapidly as ACh it continues to occupy the receptor/AChRs to “desensitize” the end-plate. Flaccid paralysis
The muscle is no longer responsive to ACh released by the motoneurons. At this point, full neuromuscular block has been achieved.
Hydrolysed by circulating esterases
therpeutic use of succinylcholine
surgery -given continuous iv short acting (minutes)
how does a depolarising neuromuscular blocking agent work?
depolarizes the motor end plate- Succinylcholine is the only such drug used clinically
Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle fibre similar to ACh.
- these agents are more resistant to degradation by acetylcholinesterase=can thus more persistently depolarize the muscle fibres.
- differs from ACh, which is rapidly degraded and only transiently depolarizes the muscle.
what are the adverse effects of succinylcholine
when administrated with halothane (anethstic) genetically susceptible people experience malignant hyperthermia
give examples cholinesterase inhibitors
Neostigmine,
edrophonium
how do acetlycholisterase inhibitors work
inhibit enzyme from breaking down acetylcholine = increasing both level and duration of NT acetlycholine
whats the mechanism of acetlycholinesterase inhibitos
Inhibits AChE- stop breakdown of ACH
what do Acetylcholinesterase inhibitors used to medicinally to treat
- Myasthenia gravis – where they are used to increase neuromuscular transmission.
- To treat glaucoma
- To treat postural tachycardia syndrome
- As an antidote to anticholinergic poisoning
what is the therapeutic use of acetlycholinesterase inhibitors?
- Antidote for non depolarising blockers such as Tubocurarine
- Treatment for myasthenia gravis (neostigmine)
- Diagnosis of myasthenia gravis (edrophonium)
what are the adverse effects of acetylcholinesterase inhibitors?
- actions on parasympathetic nervous system
- may cause bradycardia
- hypotension
- diarrhoea and vomiting
give examples of 3 nerve agents
- Sarin
- VX
- Novichok
what are immediate symptoms of nerve agents
- Runny nose
- Watery eyes
- Drooling
- Constriction of pupils
- Eye pain
- Difficultly breathing
- Confusion
- Muscle weakness
- Blockade of respiratory system -might not see earlier symptoms
what are sevre symptoms of nervre agents
- Nausea and vomiting
- Chest pain,
- shortness of breath, collapse
- seizures
- death (asphyxia)
what is the antidote to nerve agents
atropine
what do tetanus and botulinum toxins do
- reduce probability of NT release by preventing vesicles binding to pre-synaptic membrane.
Botulin- used as botox
what does tetrodotoxin do
binds to Na+ channel to block activation
what does tubocurarine do
binds to nACh receptors-stops Ach from binding- used as arrow poison
what happens in lambert-eaton syndrome
Presynaptic –reduced ACh release
- Rare autoimmune response which inhibits Ca2+ channels and thereby reduces ACh release.
- Antibodies to calcium channels
- About half patients have “small cell lung cancer” – -May have no respiratory problem but feel weak ect
whats the presentation of lambert eaton syndrome
Characterized by fatigue, weakness in limb muscle groups, autonomic dysfunction, and abnormal reflexes.
Does not usually effect respiratory, facial or eye muscles- usually effects arm and legs.
Dry mouth
Symptoms almost always precede detection of cancer - patients rarely complain of lung issues.
how do we diagnose lambert-eaton syndrome
-Electromyography (EMG) – apply electrical impulses to nerves and measuring the electrical response of the muscle. CMAP unusually small but incremental response to repetitive nerve stimulation.
-Small amplitude= less ach
-Upon repeated stimulation =ncan build up muscle AP
Symptoms usally worse in morinign and better when they become more and more active
Clinical and laboratory findings, chest x-ray for a possible lung malignancy, antibodies tocalcium channels.
Often symptoms worse in the morning
how do we treat lambert-eaton syndrome
If there is an underlying malignancy- its treatment resolves the symptoms.
Use of immunosuppressant’s such as corticosteroids
Amifampridine –drug which blocks K+ channel so action potential duration is increased, so more ACh released.
what are pennate muscles?
feather like arrangement of fascicles (fibre bundles)
give the name and location of a unipennate muscle
palmar interosseous in the hand
give the name and location of a bipennate muscle
rectus femoris in the thigh
give the name and location of a multipennate muscle
deltoid in the shoulder
what are fusiform muscles?
spindle-shaped
give the name and location of a fusiform muscle
bicep brachi in upper arm
what are parrallel muscles?
fasicles lie parrallel to the long axis of the muscle - flat muscles with parallel fibres often have aponeuroses
give the name and location of a parallel muslce
rectus abdominis ie six pack
what are convergent muscles?
broad attachment from which the fascicles converge to a single tendon
give the name and location of a convergent muscle
pectoralis major on the chest
what are circular muscles?
surround a body opening or orifice, constriciting it when contracted
give the name and location of a circular muscle
orbicularis oculi in the eye
give the main features of skeletal muscle cells
- striated
- multinucleated
- voluntary
- non-branching
- attatched to the skeleton
give the main features of cardiac muscle
- striated
- single nucleus
- involuntary
- branched
- heart muscle
give the main features of smooth muscle
- non-striated
- single nucleus
- involuntary
- tapered
- forms walls of organs
what is the epimysium?
a sheath of fibrous elastic tissue surrounding a muscle
what is the perimysium?
the sheath of connective tissue surrounding a bundle of muscle fibres
what is the endomysium?
connective tissue that covers each single muscle fiber or myofiber or muscle cell
give the structure of a muscle from largest to smallest
- muscle surrounded by epimysium (several fascicles)
- fasciculus surrounded by perimysium
what are the skeletal muscles attached to?
bones
40% body weight
what is the skeletal muscle responsible for?
locomotion (ability to move from one place to another)
facial expressions
posture
respiratory movements, other types of body movement
is skeletal muscle under voluntary or involuntary action?
Voluntary in action; controlled by somatic motor neurons
where is the smooth muscle found?
walls of hollow organs blood vessels eye glands uterus skin
what are the functions of the smooth muscle
propel urine,
mix food in digestive tract, dilating/constricting pupils, regulating blood flow
is smooth muscle autorhythmic
only in some locations
is smooth muscle voluntary or involuntary
Controlled involuntarily by endocrine and autonomic nervous systems
why is the cardiac muscle important
- unique
- for the heart so major source in the movement of blood
is the cardiac muscle autorythmic?
yes- beats on its own
is the cardiac muscle controlled involuntariliy?
yes
by endocrine and autonomic nervous systems
what kind of muscle is the cardiac muscle?
specialised form of skeletal muscle
what is the key structures of the cardiac muscle
- striated: like skeletal muscle banding - fibre length shorter
- Branched – not a single fine filament
- Interconnected- inter connected disc joins 2 cardiac myocytes together
is the cardiac or skeletal muscle cells smaller?
Cardiac smaller than skeletal muscle cells (100m x 15m, up to 10cm x 100 m)
what molecules is cardiac muscle rich in?
Rich in glycogen, myoglobin, mitochondria.
what layer do the myocardia cells produce?
myocardium
what are the characteristic bands in the cardiac muscle?
characteristic A and I bands;
Contains actin and myosin myofilaments
how many nuclei does each cell contain?
Each cell usually contains 1-2 centrally located nuclei
what are intercalated disks of cardiac muscles?
specialized cell-cell contacts.
Cell membranes interlock
what is mechanical coupling?
Joining one myocyte to the next
Desmosomes hold cells together
what is electrical coupling?
Gap junctions allow action potentials to spread quickly to adjoining cells.
what are gap junctions and which direction do molecules move in them?
Gap junction allows for electrical continuity between 2 myocytes - for AP to spread between cardiac cells by permitting the passage of ions between cells= depolarisation of heart muscle
Gap junctions are bi directional- ions move in either directions
what is another word for desmosomes
Macula adherens
what are fasica adherens
Actin anchoring sites and connect to the closest sarcomere
actin anchoring to the wall
what are desmosomes
stop separation during contraction by bindingintermediate filaments, joining the cells together.
what do autorhythmic cells do?
-initiate cardiac muscle AP:Contraction of cardiac muscle is not initiated by nerves as in skeletal muscle instead The autonomic system
- No stable resting membrane potential; neural input not necessary to initiate an AP
- Pacemaker activity instead: Slow depolarization, drift to threshold, then firing
how does an AP spread throughout the heart?
- SA node in right atrium main one = initiates cardiac contraction
- some autorhymic cells are leaky so start to depolarise and generate AP
- AP moved due to gap junction = signal spreads throughout the heart.
what are the 2 types of heart cell?
- Contractile myocardium cells
- Autorhythmic myocardium cells
what do contracile cells do?
- Myocytes contract the heart
- Do not initiate their own AP
how do autorhythimic cells work?
Fibers spontaneously contract (sino atrial node - Pacemaker cells)
what is the functional syncitium
- wave on contraction passes throughout the heart
- allows for cardiac muscle of the atria and of the ventricles behaves as single unit electrically
how do cardiac arrythmias happen?
autorhymic cells can become leaky if signals start travelling both ways in a bidirectional gap junction
= electrical instability as some myocytes become damaged
what is the membrane potential for: a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
a) -70mV
b) -90mV
c) -60mV
how is threshold potential reached in a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
a- net Na+ entry through ACh operated channels
b- depolarization enters via gap junctions
c- net Na+ entry through channels reinforced by Ca2+ entry
what is repolarisation caused by in a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
a) rapid-K+
B)extended plateu caused by Ca2+ entry - rapid phase by K+
c) rapid- K+entry
which cell hyperpolarises a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
skeltal muscle due to excessive K+
b) non as resting potential is -90
c) normally non - when repolarisation hits (-60) channels open again- can hyperpolarise the cell
how long is the refractory period in a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
a) generally brief
b) long= resetting of Na+ channels delayed until end of AP
c) none
what is conduction of pacemaker potential?
from nodal tissue to adjacent contractile cells and beyond, through gap junctions in intercalated disks
what is WPW syndrome a consequence of
several disorders of the conduction system of the heart that are commonly referred to as pre-excitation syndromes
caused by the presence of an abnormal accessory electrical conduction pathway between the atria and the ventricles = Electrical signals travelling down this abnormal pathway (known as the bundle of Kent) may stimulate the ventricles to contract prematurely, =supraventricular tachycardia/ atrioventricular reciprocating tachycardia.
= arrythmias
what is the AV node
the only electrical communication between the atria and the ventricles. It is characterized by very slow electrical conduction, ensuring that atrial contraction is completed before the ventricles are activated.
explain the 5 phases of ventricular action
depend on permeability of different ions
-Phase 0 -Cell Depolarisation; greatly increased membrane permeability to Na+ ions, which rush in through fast channels, reversing cell polarity (fast current). – rapid influx of sodium ion - accounts for rapid upstroke
-Phase 1 -Partial Repolarisation; loss of Na+ conductance, & decrease in K+ conductance.
Phase 2 -Plateau; due to the slow inward flow of Ca2+ ions through slow channels also some inward movement of Na+ through slow channels and a decrease in membrane K+ conductance. – decreasing permability to K+
Phase 3 -Repolarisation; decreased Ca2+ conductance and increased K+ conductance; inside of cell again becomes (-) relative to outside; Na+/K+ pump re-establishes distribution of ions.
Phase 4 - the interval between action potentials when the ventricular muscles are at their stable resting membrane potential.- back at resting potential
what are the classes of antiarrhythmics based on
their site of action
is the refractory period of the skeletal or cardiac muscle longer?
- Skeletal muscle action potential short refractory period (10ms)compared to the amount of time needed for development of tension
- skeletal muscle twitch is long in comparison:Cardiac muscle long refractory period as long as the muscle twitch
what is the tetanus of skeletal muscles?
-skeletal muscles that are stimulated repeatedly will exhibit summation and tetanus
-Once outside refractory period can stimulate skeletal muscle again even though muscle is contracted
= bigger tension being build up = max tension
how long does the ventricular AP last?
- lasts almost as long as entire muscle twitch
- 250ms
- long refractory period in cardiac muscle prevents tetanus as dont stimulate again so quickly
- allows heart to fill up with blood
explain how the cardiac excitiation-contraction coupling works
1- AP invades the T-tubules and Ca2+ enters through L-type Ca2+ channels
2- triggers further Ca2+ release from adjacent sarcoplasmic reticulum = amplifies Ca2+
3- ‘calcium-induced calcium release’ = small influx of calcium = cascade effect = further release of Ca from sarcoplasmic reticulum
4- Ca2+ binds to troponin-C to initiate contraction-now- proceeds in the same way as in skeletal muscle
5- contraction
6- relaxation occurs within Ca2+ unbinds from troponin
7- Ca2+ pumped back into the sarcoplasmic reticulum for storage
8- Ca2+ is exchanged with Na+
9- Na+ gradient is maintained by sodium potassium pump
how do we ensure tight control of cardiac excitiation-contraction coupling works
Each L-type channel appears to control only one SR release channel, due to the local structure, this means tight local control
how does noradrenaline effect the heart
Noradrenaline increases the contractile force of the heart. It acts through the beta-type adrenergic receptor to increase cAMP, to activate PKA which phosphorylates the L-type channel, increasing passive Ca2+ influx
what is digoxin
‘foxglove’
treatment for heart failure
inhibit Na/K ATP ase pump
by what mechanism does digoxin work?
- involves inhibition of the sodium potassium adenosine triphosphatase (Na+/K+ ATPase) in myocardium
- inhibition= increase in intracellular Na = reversal of action of Na/Ca exchanger (important 3 Na in and 2 a out)
- increase intracellular Ca
- lengthens phase 4 and 0= decrease in heart rate
- also get increased Ca in SR =increased release of Ca during each AP = increased contractility
whats the resting potential in the cardiac cells
SA node - no stable resting membrane potential due to slow influx of Ca2+
whats the pacemaker polarisation
gradual depolarization from -60 mV, slow influx of Ca2+, reduced K+ permeability
at what voltage does the stages leading to AP happen in cardiac muscle
Action potential
-occurs at threshold of -40 mV
-depolarizing phase to 0 mV:
Due to fast Ca2+ channels open, (Ca2+ in)
-repolarizing phase
K+ channels open, (K+ out)
at -60 mV K+ channels close, pacemaker potential starts over
-Each depolarization creates one heartbeat
what molecule causes the depolarisation in the SA node
Calcium influx (rather than sodium) for rising phase of the action potential
whats the effect of acetylcholine from the parasympathetic nerves
- Stimulate vagus nerve (parasympathetic control)
- Decrease SA node rate
- Decrease heart rate
whats the effect of Noradrenaline from sympathetic nerves
- Raise threshold
- Opening of calcium channels earlier= increase heart rate
- Increases rate of depolarisation of pacemaker cells of SA node
- Develop action potentials at an increased rate
- Increase heart rate
what is the ‘optimum level’ for the length of the cardiac muscle cells?
. when the heart is in diastole, the degree of overlap between the thick and thin filaments in the ventricular muscle cells is less than optimal
why is the ‘optimum level’ for the length of the cardiac muscle cells important?
up to a point, stretching the cells more will result in a greater degree of myosin–actin overlap and, therefore, in an increase in the amount of force generated when the cells contract
so when we hit optimum levels decline
what is the structure of smooth muscle
-2 Sheets of closely opposed fibers
-circular layer and tubule layer which allows pushing of smooth muscle cells/ the lumen
2 sheets :
inner circular
Outer longitudinal
Only capillaries don’t have smooth muscle
what is peristalsis
Alternating contraction relaxation of the 2 layers mixes substances in lumen of hollow organs
describe the ultrastructure of the smooth muscle
-Fibers smaller than those in skeletal muscle
-Spindle-shaped; single
-central nucleus
- Not straited
-More actin than myosin (16:1 in skeletal 2:1)
No sarcomeres
-No T-tubules and the sarcoplasmic reticulum is poorly developed
-Caveolae: indentations in sarcolemma;
May act like T tubules- influx or conduction through them if AP
-actin attached to dense bodies - myosin sites
how are the thick and thin filaments arranged in smooth muscle
- Thick and thin filaments not well organised (unlike skeletal muscle), thus NO striations.- tends to spiral down length of cell
- When cell contracts= corkscrew motion pulling in the cell
- The thick and thin filaments appear to spiral down the long axis of the cell, so the cell contracts in a corkscrew-like way
what are the skeletal muscles attached to?
bones
40% body weight
what is the skeletal muscle responsible for?
locomotion (ability to move from one place to another)
facial expressions
posture
respiratory movements, other types of body movement
is skeletal muscle under voluntary or involuntary action?
Voluntary in action; controlled by somatic motor neurons
where is the smooth muscle found?
walls of hollow organs blood vessels eye glands uterus skin
what are the functions of the smooth muscle
propel urine,
mix food in digestive tract, dilating/constricting pupils, regulating blood flow
is smooth muscle autorhythmic
only in some locations
features of single unit (unitary) smooth muscles?
- most common
- all the smooth cells joined together by gap junction = act as single unit
- arthymic
- have own pacemaker cells
why is the cardiac muscle important
- unique
- for the heart so major source in the movement of blood
is the cardiac muscle autorythmic?
yes- beats on its own
why is Single-Unit Smooth Muscle described as a myogenic response?
They contract in response to stretch
what kind of muscle is the cardiac muscle?
specialised form of skeletal muscle
what is the key structures of the cardiac muscle
- striated: like skeletal muscle banding - fibre length shorter
- Branched – not a single fine filament
- Interconnected- inter connected disc joins 2 cardiac myocytes together
is the cardiac or skeletal muscle cells smaller?
Cardiac smaller than skeletal muscle cells (100m x 15m, up to 10cm x 100 m)
what molecules is cardiac muscle rich in?
Rich in glycogen, myoglobin, mitochondria.
what layer do the myocardia cells produce?
myocardium
what are the characteristic bands in the cardiac muscle?
characteristic A and I bands;
Contains actin and myosin myofilaments
how many nuclei does each cell contain?
Each cell usually contains 1-2 centrally located nuclei
what are intercalated disks of cardiac muscles?
specialized cell-cell contacts.
Cell membranes interlock
what is mechanical coupling?
Joining one myocyte to the next
Desmosomes hold cells together
what is electrical coupling?
Gap junctions allow action potentials to spread quickly to adjoining cells.
what are gap junctions and which direction do molecules move in them?
Gap junction allows for electrical continuity between 2 myocytes - for AP to spread between cardiac cells by permitting the passage of ions between cells= depolarisation of heart muscle
Gap junctions are bi directional- ions move in either directions
what is another word for desmosomes
Macula adherens
what are fasica adherens
Actin anchoring sites and connect to the closest sarcomere
actin anchoring to the wall
what are desmosomes
stop separation during contraction by bindingintermediate filaments, joining the cells together.
what do autorhythmic cells do?
-initiate cardiac muscle AP:Contraction of cardiac muscle is not initiated by nerves as in skeletal muscle instead The autonomic system
- No stable resting membrane potential; neural input not necessary to initiate an AP
- Pacemaker activity instead: Slow depolarization, drift to threshold, then firing
how does an AP spread throughout the heart?
- SA node in right atrium main one = initiates cardiac contraction
- some autorhymic cells are leaky so start to depolarise and generate AP
- AP moved due to gap junction = signal spreads throughout the heart.
what are the 2 types of heart cell?
- Contractile myocardium cells
- Autorhythmic myocardium cells
what do contracile cells do?
- Myocytes contract the heart
- Do not initiate their own AP
how do autorhythimic cells work?
Fibers spontaneously contract (sino atrial node - Pacemaker cells)
what is the functional syncitium
- wave on contraction passes throughout the heart
- allows for cardiac muscle of the atria and of the ventricles behaves as single unit electrically
how do cardiac arrythmias happen?
autorhymic cells can become leaky if signals start travelling both ways in a bidirectional gap junction
= electrical instability as some myocytes become damaged
what is the membrane potential for: a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
a) -70mV
b) -90mV
c) -60mV
how is threshold potential reached in a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
a- net Na+ entry through ACh operated channels
b- depolarization enters via gap junctions
c- net Na+ entry through channels reinforced by Ca2+ entry
what is repolarisation caused by in a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
a) rapid-K+
B)extended plateu caused by Ca2+ entry - rapid phase by K+
c) rapid- K+entry
which cell hyperpolarises a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
skeltal muscle due to excessive K+
b) non as resting potential is -90
c) normally non - when repolarisation hits (-60) channels open again- can hyperpolarise the cell
how long is the refractory period in a)skeletal muscle, b)contractile myocardium, c)autorhythmic myocardium
a) generally brief
b) long= resetting of Na+ channels delayed until end of AP
c) none
what is conduction of pacemaker potential?
from nodal tissue to adjacent contractile cells and beyond, through gap junctions in intercalated disks
what is WPW syndrome a consequence of
several disorders of the conduction system of the heart that are commonly referred to as pre-excitation syndromes
caused by the presence of an abnormal accessory electrical conduction pathway between the atria and the ventricles = Electrical signals travelling down this abnormal pathway (known as the bundle of Kent) may stimulate the ventricles to contract prematurely, =supraventricular tachycardia/ atrioventricular reciprocating tachycardia.
= arrythmias
what is the AV node
the only electrical communication between the atria and the ventricles. It is characterized by very slow electrical conduction, ensuring that atrial contraction is completed before the ventricles are activated.
explain the 5 phases of ventricular action
depend on permeability of different ions
-Phase 0 -Cell Depolarisation; greatly increased membrane permeability to Na+ ions, which rush in through fast channels, reversing cell polarity (fast current). – rapid influx of sodium ion - accounts for rapid upstroke
-Phase 1 -Partial Repolarisation; loss of Na+ conductance, & decrease in K+ conductance.
Phase 2 -Plateau; due to the slow inward flow of Ca2+ ions through slow channels also some inward movement of Na+ through slow channels and a decrease in membrane K+ conductance. – decreasing permability to K+
Phase 3 -Repolarisation; decreased Ca2+ conductance and increased K+ conductance; inside of cell again becomes (-) relative to outside; Na+/K+ pump re-establishes distribution of ions.
Phase 4 - the interval between action potentials when the ventricular muscles are at their stable resting membrane potential.- back at resting potential
what are the classes of antiarrhythmics based on
their site of action
is the refractory period of the skeletal or cardiac muscle longer?
- Skeletal muscle action potential short refractory period (10ms)compared to the amount of time needed for development of tension
- skeletal muscle twitch is long in comparison:Cardiac muscle long refractory period as long as the muscle twitch
what is the tetanus of skeletal muscles?
-skeletal muscles that are stimulated repeatedly will exhibit summation and tetanus
-Once outside refractory period can stimulate skeletal muscle again even though muscle is contracted
= bigger tension being build up = max tension
how long does the ventricular AP last?
- lasts almost as long as entire muscle twitch
- 250ms
- long refractory period in cardiac muscle prevents tetanus as dont stimulate again so quickly
- allows heart to fill up with blood
explain how the cardiac excitiation-contraction coupling works
1- AP invades the T-tubules and Ca2+ enters through L-type Ca2+ channels
2- triggers further Ca2+ release from adjacent sarcoplasmic reticulum = amplifies Ca2+
3- ‘calcium-induced calcium release’ = small influx of calcium = cascade effect = further release of Ca from sarcoplasmic reticulum
4- Ca2+ binds to troponin-C to initiate contraction-now- proceeds in the same way as in skeletal muscle
5- contraction
6- relaxation occurs within Ca2+ unbinds from troponin
7- Ca2+ pumped back into the sarcoplasmic reticulum for storage
8- Ca2+ is exchanged with Na+
9- Na+ gradient is maintained by sodium potassium pump
how do we ensure tight control of cardiac excitiation-contraction coupling works
Each L-type channel appears to control only one SR release channel, due to the local structure, this means tight local control
how does noradrenaline effect the heart
Noradrenaline increases the contractile force of the heart. It acts through the beta-type adrenergic receptor to increase cAMP, to activate PKA which phosphorylates the L-type channel, increasing passive Ca2+ influx
what is digoxin
‘foxglove’
treatment for heart failure
inhibit Na/K ATP ase pump
by what mechanism does digoxin work?
- involves inhibition of the sodium potassium adenosine triphosphatase (Na+/K+ ATPase) in myocardium
- inhibition= increase in intracellular Na = reversal of action of Na/Ca exchanger (important 3 Na in and 2 a out)
- increase intracellular Ca
- lengthens phase 4 and 0= decrease in heart rate
- also get increased Ca in SR =increased release of Ca during each AP = increased contractility
whats the resting potential in the cardiac cells
SA node - no stable resting membrane potential due to slow influx of Ca2+
whats the pacemaker polarisation
gradual depolarization from -60 mV, slow influx of Ca2+, reduced K+ permeability
at what voltage does the stages leading to AP happen in cardiac muscle
Action potential
-occurs at threshold of -40 mV
-depolarizing phase to 0 mV:
Due to fast Ca2+ channels open, (Ca2+ in)
-repolarizing phase
K+ channels open, (K+ out)
at -60 mV K+ channels close, pacemaker potential starts over
-Each depolarization creates one heartbeat
what molecule causes the depolarisation in the SA node
Calcium influx (rather than sodium) for rising phase of the action potential
whats the effect of acetylcholine from the parasympathetic nerves
- Stimulate vagus nerve (parasympathetic control)
- Decrease SA node rate
- Decrease heart rate
whats the effect of Noradrenaline from sympathetic nerves
- Raise threshold
- Opening of calcium channels earlier= increase heart rate
- Increases rate of depolarisation of pacemaker cells of SA node
- Develop action potentials at an increased rate
- Increase heart rate
what is the ‘optimum level’ for the length of the cardiac muscle cells?
. when the heart is in diastole, the degree of overlap between the thick and thin filaments in the ventricular muscle cells is less than optimal
why is the ‘optimum level’ for the length of the cardiac muscle cells important?
up to a point, stretching the cells more will result in a greater degree of myosin–actin overlap and, therefore, in an increase in the amount of force generated when the cells contract
so when we hit optimum levels decline
what is the structure of smooth muscle
-2 Sheets of closely opposed fibers
-circular layer and tubule layer which allows pushing of smooth muscle cells/ the lumen
2 sheets :
inner circular
Outer longitudinal
Only capillaries don’t have smooth muscle
what is peristalsis
Alternating contraction relaxation of the 2 layers mixes substances in lumen of hollow organs
describe the ultrastructure of the smooth muscle
-Fibers smaller than those in skeletal muscle
-Spindle-shaped; single
-central nucleus
- Not straited
-More actin than myosin (16:1 in skeletal 2:1)
No sarcomeres
-No T-tubules and the sarcoplasmic reticulum is poorly developed
-Caveolae: indentations in sarcolemma;
May act like T tubules- influx or conduction through them if AP
-actin attached to dense bodies - myosin sites
how are the thick and thin filaments arranged in smooth muscle
- Thick and thin filaments not well organised (unlike skeletal muscle), thus NO striations.- tends to spiral down length of cell
- When cell contracts= corkscrew motion pulling in the cell
- The thick and thin filaments appear to spiral down the long axis of the cell, so the cell contracts in a corkscrew-like way
explain the mechanism of contraction in smooth muscle
- Contraction depends on an increase in cytosolic Ca2+
- Ca2+ binds to calmodulin (not troponin) interacts with enzyme myosin kinase to phosphorylate myosin at a specific site on the myosin ‘light chain’ . Units and cause contraction
- Formation of cross bridge and contraction
- Once phosphorylated generates tension by attaching to actin filament in a similar way as occurs in skeletal muscle
- When the cytoplasmic Ca2+ falls, the Ca2+-calmodulin complex dissociates, inactivating myosin kinase.
- The cross bridges are dephosphorylated by the enzyme myosin phosphatase.
is dephosphorlaytion a long or slow process
slow
why is contraction in smooth muscle not regulated by the thin filament
because it lacks troponin - unlike skeletal and cardiac muscle
what is an important feature of smooth muscle
- its ability to maintain force over long periods of time (eg Sphincters).
- Cross bridge cycling is much slower. Hence, contraction of smooth muscle occurs more slowly and the duration of the contraction in response to a stimulus is long.
- Reduced ATP consumption.
why is cross bridge cycling in smooth muscle much slower?
- Smooth muscle myosin has a slow ATPase rate, so once attached, it takes a long time for each cross bridge to detach from the actin filament.
- The rate of Ca2+removal from the cytoplasm is slow, so prolonging the duration of contraction.
does smooth muscle receive input from more than one nerve?
yes
features of single unit (unitary) smooth muscles?
- most common
- all the smooth cells joined together by gap junction = act as single unit
where are Single-Unit Smooth Muscle located?
gastrointestinal, respiratory, urinary and reproductive tracts, and in the walls of small arteries
how does electrical activity arise in Single-Unit Smooth Muscle
arise spontaneously due to the presence of ‘pacemaker’ cells. Action potentials are developed
-Nervous regulation is via the autonomic nervous system
why is Single-Unit Smooth Muscle described as a myogenic response?
They contract in response to stretch
what are varicosities?
Autonomic nerves make multiple contacts with the cell
how are receptors organised in Single-Unit Smooth Muscle
- receptors spread across cell membrane.
- No specialised post junctional membrane
features of Multi-Unit Smooth Muscle
- Allows fine control, examples include ciliary muscle of the eye controlling size of pupil and piloerector muscles of hair follicles.
- Not spontaneously active.
- Innervation is autonomic
- There is no inherent response to stretch
- Contractions are slow and sustained
do multi-unit smooth muscle has gap junction
Lack gap junction, cells innervated individually.
- individual muscles are controlled
do smooth muscle have post synaptic structures
Specialised Post Synaptic structure NOT present in Smooth Muscle- just varicosities
what happens in dilated cardiomyopathy
- Sudden death
- Heart enlarges, functions poorly
- Muscle becomes weak, inefficient causing fluid build up in the lungs, → breathlessness → left heart failure
- Right heart failure → fluid build up in tissues & organs (legs, ankles, liver, abdomen)
- Thinning of ventricular wall
- And enlargement = heart start to function poorly = congestion of fluid in lugs breathlessness
what are the symptoms of dilated cardiomyopathy
Shortness of breath Swelling of the ankles Tiredness Palpitations and Syncope Chest pain
what are the causes of dilated cardiomyopathy
- Viral Infection
- Auto-Immune Disease
- Excessive alcohol consumption/exposure to toxic compounds
- Pregnancy
- Familial disease
what is hypertrophic cardiomyophathy
Thickening of muscle; may thicken in normal individuals as a result of high blood pressure or prolonged athletic training.
what is the cause of HCM
without obvious cause
what is myocardial disarray in HCM
Normal alignment of muscle cells is absent
Who is HCM more common in
young adults
Prognosis variable- many stable for years
can occur without individuals knowing
what happens in HCM
- Septum that will enlarge = no obstruction of blood flow so no reported symptoms
- As septum begins to enlarge more = obstructed flow = impeachment of blood flow though heart
- Prior to symptoms no symptoms
- Symmetrical hypertrophy= ventricle wall and septum enlarge = no symtpoms
- Hypertrophic cardiomyopathyis a disease of themyocardium in which a portion of the myocardium ishypertrophied (thickened) without any obvious cause
what are the symptoms of HCM
Shortness of breath
Chest pain
Palpitation
Light-headedness and blackouts
what are the causes of HCM
Genetic mutation, of important proteins for the contraction of the heart- ones that involved in desdomond and hold mechanical connection between myocytes
outline features of leiomyoma (fibroids)
Benign growth
Female reproductive tract
Usually multiple, diameter 5mm upwards
More prevalent approaching menopause
Heavy uterine bleeding &/or pain
Cause unknown, associated factors include genetic factors
