Nerves and muscles Flashcards
1
Q
Divisions of the nervous system
A
Central Nervous System (CNS)
• Brain
• Spinal cord
Peripheral Nervous System (PNS): 2 Divisions
Somatic Nervous System
Autonomic Nervous System (ANS)
(1) Sympathetic
(2)Parasympathetic
(3) Enteric
2
Q
Neurones- Characteristics
A
- High metabolic rate
- Brains – ‘grey matter’
- Many dendrites – signal inputs
- One axon – signal conduction
- Many synaptic terminals – signal output
3
Q
Structural classes of neurones- 3 of them
A
Multipolar neurone (a single long axon and many dendrites emerging from cell body- motorneurones)
Unipolar neurone (pseudo-unipolar) (found in sensory ganglia)
Bipolar neurone (found in sensory structures e.g. retina)
4
Q
Organisation within the spinal cord
A
White matter mostly contains myelinated axons, and grey matter mostly cell bodies, this accounts for the different staining.
5
Q
What happens when white and grey matter is stained with Weigert’s stain (stains myelin)
A
White matter stains dark- has most myelin as mostly axons
Grey matter stains pale- as mostly cell bodies.
6
Q
What is a group of nerve cells called in the CNS and PNS?
A
A group of nerve cells is called a nucleus in the CNS but a ganglion in the PNS.
7
Q
What is a bundle of axons called in the CNS and PNS?
A
A bundle of axons in the CNS is a tract, in the PNS a nerve.
8
Q
What are ganglia? What types are there in the PNS?
A
Ganglia are neuronal cell bodies (ganglion cells) & supporting neuroglia (satellite cells)
Two types of ganglia in the PNS:
• sensory ganglia: cell bodies of sensory (afferent) neurons
• autonomic ganglia: cell bodies of motor (efferent) neurons from the autonomic nervous system
9
Q
Structure of peripheral nerves
A
Three layers of connective tissue around the myelin sheath of each myelinated nerve fibre.– epineurium (covers the whole nerve), perineurium (covers a fascicle) and endoneurium (covers individual nerve axons).
10
Q
What are neurolgia and what do they do?
A
Neuroglia (Glia or Glial cells)
Traditionally considered as supporting cells for neurones
Recent work – regulate neurone metabolism & function (energy supply & transmitter levels)
Repair & recovery from injury
Regulate blood-brain barrier
Destroy pathogens and remove dead neurones
11
Q
Glial cell dysfunction implicated in neurological disorders- examples
A
Autism, schizophrenia or neurodegeneration
12
Q
Main types of neurolgia in the CNS
A
Astrocytes- involved in metabolic exchange between neurons and blood
Oligodendrocytes- myelinate axons
Microglia- immune defence- become phagocytic
Ependyma- lining cells or ventricles and central spinal canal, produce CSF
13
Q
Neurodegenerative problems
A
- MS (multiple sclerosis)
- ALD (adrenoleukodystrophy)
- ALS (motor neurone disease)
14
Q
Main types of neuroglia in the PNS- Schwann cells
A
Schwann cell: similar in function to oligodendrocytes i.e. the Schwann cells provide myelination to axons in the peripheral nervous system (PNS). They also have phagocytotic activity and clear cellular debris that allows for regrowth of PNS neurons.
15
Q
Main types of neuroglia in the PNS-Satellite cells
A
Satellite cells - small cells that surround neurons in sensory, sympathetic, and parasympathetic ganglia. These cells help regulate the external chemical environment. They are similar to astrocytes and are highly sensitive to injury and inflammation.
16
Q
Process of Myelination
A
Myelination of axons
- Oligodendrocytes myelinate in CNS; Schwann cells myelinate in PNS
- Wrap axon in spiral of concentric layers of fatty myelinated membrane
- Insulation for axons to aid impulse transmission
- Gaps between adjacent cells – Nodes of Ranvier
17
Q
Non-myelinated axons
A
Non-myelinated nerves have a supporting Schwann cell
Axon is embedded in a channel called the mesaxon, where the Schwann cell is right next to the axon.
A single Schwann cell supports several axons
18
Q
Demyelinating Diseases consequences
A
- A demyelinating disease –a condition that results in damage to the myelin sheath
- Consequences of myelin damage: nerve impulses slow/stop, causing neurological problems
- Deficiency in sensation, movement, cognition, or other functions specific to the nerves involved
- Extensive myelin loss is usually followed by axonal degeneration and often cell body degeneration
19
Q
Classification of demyelinating diseases- Demyelinating myelinoclastic diseases and demyelinating leukodystrophic (dysmyelinating) diseases
A
Divided on basis of the cause
- Demyelinating myelinoclastic diseases – secondary: healthy myelin is destroyed by a toxic (eg, alcohol), infectious agents, chemical or autoimmune substance
- Demyelinating leukodystrophic (dysmyelinating) diseases – primary: myelin is abnormal and degenerates; caused by genetics, some idiopathic.
20
Q
What is MS
A
• Common demyelinating disease of the CNS
• Aetiology – autoimmune in nature
• Environmental/genetic factors lead to loss of tolerance to self-proteins
• Inflammation and injury to the myelin sheath and nerve fibres
-multiple areas of scarring (sclerosis i.e. lesions/plaques).
• Physical, mental, psychiatric problems
21
Q
What is the somatic NS?
A
- often called voluntary nervous system
- has somatic motor neurones- efferent motor neurones/ motoneurones
- innervates and controls voluntary, striated muscles
- has sensory neurones- sensory afferent neurones
22
Q
What is the autonomic NS?
A
• Involuntary nervous system. • Controls: – heart rate – blood pressure – respiration – sweat glands – gut movements
• Sympathetic-speeds things up • Parasympathetic-calms things down – anatomical and functional divisions – antagonistic actions – both have efferent (motor) and afferent (sensory) components
23
Q
Classification of Nerve Fibres
A
Systems based on fibre diameter and conduction velocity (how fast the impulses travel down the axon)
24
Q
Classification of sensory receptors
A
- By location within the body.
• Exteroceptors – external surface
• Interoceptors – internal organs
• Proprioceptors – internal, but concerned with position of muscles, tendons, joints. - By stimulus type detected.
• Mechanoreceptors – touch, pressure, vibration, stretch
• Thermoreceptors – hot, cold, temperature change
• Photoreceptors - light
• Chemoreceptors – chemicals
• Nociceptors – pain (usually chemicals)
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Spinal cord reflex pathway
1. Sensory receptor - site of stimulus action
2. Sensory neurone - transmits afferent information to the CNS
3. Integration centre - one or more synapses within CNS (may also signal up to brain)
4. Motor neurone - conducts efferent impulses to the effector organ
5. Effector - muscle fibre (or gland) that responds to impulses
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4 factors that contribute to the resting membrane potential
1. charged intracellular proteins- large negative charged proteins trapped in cell- negative cell compared outisde
2. the Na+/K+ pump- 3 Na ions out cell, 2 K ions in cell. Cell becomes more negative
3. potassium ions- 2 K in cell but large negative gradient cell drags back K
4. sodium ions- inward flow Na- cell becomes more positive
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Factors that contribute to the resting membrane potential- Effect of intracellular proteins
Large negatively charged intracellular proteins cannot cross the cell membrane to leave the cell interior and so contribute to its negativity.
Large protein molecules within the cytoplasm of the cell are too big to pass through channels in the membrane and have a predominance of negatively charged groups on their surface. This lack of membrane permeability means they are trapped within the cell and cause it to be negatively charged with respect to the extracellular fluid.
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Factors that contribute to the resting membrane potential- Effect of the sodium/potassium ion pump
The Na+/K+ pump moves 3 Na+ ions out for every 2 K+ ions in. Thus inside of the cell gets more negative.
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Factors that contribute to the resting membrane potential- Effect of potassium ion gradients
K+ tends to leak out of the cell down [gradient], but cell’s negative charges inside tend to pull K+ back in. Eventually, in theory, fluxes become balanced so K+ distribution will be in equilibrium.
Although the concentration gradient for K+ ions means that they tend to diffuse out of the cell through the K+ selective channels, the large negatively charged protein molecules trapped within the cell cause an electrical gradient, which tends to pull the K+ ions back in.
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Factors that contribute to the resting membrane potential- Effect of sodium ion gradients
The membrane is only slightly permeable to Na+, so its effects on resting potential are small. The net inward diffusion of Na+ slightly adds to the positivity of the cell.
Note that in the case of sodium ions both the concentration and electrical gradients operate in the same direction to cause inward flow of ions.
The net effect of this is to bring the resting potential back up to about -65 mV.
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Phases of the action potential
Phase 1:
• Na+ channels open
• Na+ enters nerve cell
• Membrane potential rises towards zero
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Phase 2:
Depolarisation
• If threshold potential reached, voltage gated Na+ channels open
• Na+ ions flow into cell
• Action potential spike results
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Phase 3:
Repolarisation
• Na+ channels close when Na+ equilibrium potential is reached
• Voltage gated K+ channels open and K+ ions flow out of cell
• Membrane potential reverses
Phase 4:
Hyperpolarisation
• K+ ions continue to flow out of cell while Na+ channels closed
• Hyperpolarisation results
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Steps of an AP
1. Resting state: all voltage gated Na+ and K+ channels closed
2. Depolarising phase: Na+ channel fast activation gates open
3. Overshoot phase: inactivation gates of Na+ channels start to close and activation gates of K+ channels begin to open
4. Repolarising phase: inactivation gates of Na+ channels closed and K+ channels open
5. Undershoot phase (after potential): K+ channels still remain open, Na+ channels closed
6. Resting state: all voltage gated Na+ and K+ channels closed
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“All-or-nothing” action potential- how it works
* All excitable cells have a threshold membrane potential
* Membrane has to be depolarised beyond threshold for an AP to be generated
* Further increase above threshold -> higher AP frequency not larger AP amplitude
* A neurone either fires or it does not, regardless of signal size – “all-or-nothing”
34
Action Potential Refractory Periods- are there AP?
During the absolute refractory period no further action potentials can be elicited. This ensures action potential propagation is unidirectional. During the relative refractory period a larger stimulus can result in action potential.
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. AP can’t summate. It cannot reverberate (i.e. go backwards towards its point of origin – normally the point where the axon joins the nerve cell body).
35
Non-myelinated axon- how AP moves along
Non-myelinated axon:
Na+ influx depolarises area in front of it and triggers voltage gated Na + channels to open.
Causes AP in next membrane.
Membrane behind impulse in refractory.
Impluse can only go forward along axon.
36
Myelinated axon
Nodes of Ranvier are the only areas where current can pass through membrane.
Nodes are only areas where membrane can depolarise.
Impulse travels in 'jump' not slow flow.
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Sensory receptors
Sensory neurone endings, often modified to form specialised sensory receptors, which are ‘tuned’ to specific signals or sensory modalities, i.e., different forms of energy (light, vibration, chemicals, etc.). Sensory transduction is the conversion of environmental or internal signals into electrochemical energy.
Detection of stimulus by receptor causes a receptor potential
• Graded electrotonic response (not action potential)
• Causes action potential
• Specific signals – rate and pattern of action potential firing – decoded in CNS
38
Sensory receptors in muscles
Where is the muscle spindle located?
Where is the Golgi Tendon Organ located?
* Both are proprioceptors and mechanoreceptors
* The muscle spindle is located within the muscle and stimulated when the muscle is passively stretched.
* The Golgi Tendon Organ is located in the tendon and responds to tension (it is stimulated when associated muscle contracts or is stretched).
39
Muscle spindle- what is it needed for?
* When a muscle is stretched passively the spindle is activated and so initiates a reflex
* When the muscle contracts and shortens it is switched off
* Protects muscle being overstretched
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Golgi Tendon Organ- what is it for?
* GTO is active during both passive stretch and active contraction
* It is a tension detector that protects muscle against excess load
* Function to protect the muscle and connective tissue from injury
* Stimulated by excessive tension during muscle contraction or passive stretch
* Causes a reflex inhibition of the muscle-relaxation
* Helps prevent excessive muscle contraction or passive muscle stretch i.e. Inverse stretch reflex
41
Two types of synapses- what are they?
Neurones communicate via synapses (synaptic junctions) of which there are 2 types:
• Electrical synapses – direct passage of current via ions flowing through gap junctions
• Chemical synapses – release of vesicles containing chemical transmitter which has an effect on receptors on a target cell
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Electrical synapse- how are they formed?
Formed by interlocking connexon channels of adjacent neurones. Connexons comprise connexin proteins.
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How do chemical synapses for?
* 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
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Neurotransmitter
Neurotransmitter- a substance that is released at a synapse by one neurone that affects another cell, either neuron or effector organ, in a specific manner
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Neuromodulator
Neuromodulator – a substance that is released and modifies the action of a transmitter, but doesn’t have a direct action itself
46
Neuroactive substance
Neuroactive substance – a neutral term if a substance is known to have an effect in the CNS but its precise action is not known
47
Neurotransmitter receptor interactions- ionotrophic and metabotropic receptors
Ionotropic receptor is a cluster of similar subunits forming ion channels, that depolarise or hyper-polarise the postsynaptic cell (fast responses).
Metabotropic receptors is a 7-transmembrane molecule coupled to intracellular proteins that transduce a signal to cell interior (slow responses).
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Postsynaptic excitation
* Binding of released transmitter to a ligand-gated ion channel receptor causes opening of channel pore
* Binding of glutamate or acetylcholine to their receptors causes an influx Na+ ions giving rise to an excitatory post-synaptic potential (EPSP) in postsynaptic cell
* EPSPs depolarise cell towards threshold potential and may initiate an AP
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Postsynaptic inhibition
* Binding of GABA or glycine to their receptors causes an influx of Cl- ions giving rise to an inhibitory post-synaptic potential (IPSP) in postsynaptic cell
* IPSPs tend to hyperpolarise cell and make initiation of an AP less likely i.e. inhibition
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Excitatory Post Synaptic Potentials
* No threshold
* Decrease resting membrane potential i.e. closer to threshold for depolarization
* Graded in magnitude
* No refractory period
* Can summate
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Inhibitory Post Synaptic Potentials
* No threshold
* Hyperpolarize post synaptic membrane
* Increase membrane potential i.e. moving it further from threshold for depolarization
* No refractory period
* Can summate
52
What happens to the NTM?
1. Can be taken back up directly into neurones by transporters on the presynaptic membrane (or even postsynaptic).
2. Can be broken down by cell surface enzymes into constituent parts, which are then taken back up into neurones by transporters.
3. Can be taken up into glial cell processes lining the peri-synaptic zone by glial cell transporters, then “shuttled” back into neurones by a process involving other transporters.
4. Can be taken up into glial cell processes by glial cell transporters, broken down or converted by enzymes in the glial cells, then the resulting metabolites “shuttled” back into neurones by a process involving other transporters.
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Components of the motor unit
Motor unit:
* A motor unit consists of the motor nerve and all the muscle fibres innervated by that nerve
* All the muscle fibres within a motor unit contract together when the motor nerve fires
* Size of motor units depends on the function of the muscle
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Neuromuscular Transmission
* 1:1 transmission: A chemical transmission which is designed so that every presynaptic action potential results in a postsynaptic one
* A unidirectional process
* Has an inherent time delay
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Process of Chemical Transmission
The action potential reaches the axon terminal of the presynaptic cell – causes depolarisation of the terminal membrane
This causes opening of voltage gated calcium channels
High driving force – calcium rushes into cell through open channels
Calcium increases can trigger many different cellular cascades – only want vesicle release in this case, so microdomains serve to keep the calcium increase localised to area around vesicles only.
The action potential 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, and 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 (i.e. by increasing calcium concentration) or decreased (i.e. by blocking depolarisation of the membrane and preventing calcium influx).
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nAChR structure
Each receptor formed from 5 subunits – each subunit formed from 4 transmembrane spanning segments.
Different subunit types so different types of nAChR depending on composition.
Have 2 alpha subunits – these are the subunits with ACh binding sites – two molecules of ACh must bind to receptor before receptor is activated (one on each alpha subunit).
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Miniature End Plate Potentials (MEPPs) and EPPs
* 1 quantum = contents of 1 synaptic vesicle
* ACh released activates 1000-2000 receptors
* Depolarisation produced by single quantum of Ach- MEPP
* MEPPs are additive > becoming end plate potentials (EPPs).
* When EPPs cause the membrane to reach threshold voltage gated ion channels in the postsynaptic membrane open > influx of Na+ > action potential > leading to muscle contraction
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Life cycle of 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+. 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.
5) Ca2+ channels activated by action potential - Ca2+ influx.
6) Raised Ca2+ triggers membrane fusion and ACh release (exocytosis)
7) Release of vesicles from reserve.
8) ACh diffuses across cleft and binds to nicotinic receptor, opening channel.
9) ACh broken down to choline and acetate by acetylcholinesterase, bound mainly to basal lamina.
10) Choline taken up into nerve terminal by cotransport with Na+.
(11-14) Vesicles become part of membrane, endocytosis, clathrin coated and internalised. Fuses with endosome, new vesicles formed from budding- new cycle.
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Drugs used at the NMJ- Neuromuscular Blocking agents- Non depolarising agent
Non depolarising competitive nAChR antagonist e.g. Tubocurarine
Mechanism: Competes with ACh for nicotinic receptor binding sites - muscle paralysis occurs gradually.
Reversed by AChE inhibitors (i.e. Neostigmine)
Hydrolysed by circulating esterases
Therapeutic use: surgery
Adverse effect: decrease BP, bronchospasm
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Drugs used at the NMJ- Neuromuscular Blocking agents- Depolarising agent
Depolarising nAChR agonist e.g. Succinylcholine
Mechanism: Persistent depolarization of the neuromuscular junction.
Phase I: Membrane depolarized causing brief period of muscle fasciculation (twitching).
Phase II: End plate eventually repolarizes, but because Succinylcholine is not metabolised as rapidly as ACh it continues to occupy the receptor. Flaccid paralysis
Hydrolysed by circulating esterases
Therapeutic use:
Surgery -given continuous IV short acting (minutes)
Adverse effects: when administrated with halothane genetically susceptible people experience malignant hyperthermia
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Cholinesterase Inhibitors
Cholinesterase Inhibitors e.g. Neostigmine, edrophonium
Mechanism: Inhibits AChE
Therapeutic Use:
Antidote for non-depolarising blockers such as Tubocurarine
Treatment for myasthenia gravis (neostigmine)
Diagnosis of myasthenia gravis (edrophonium)
Adverse effects: Generalized cholinergic activation (muscarinic & nicotinic) Abdominal cramping, diarrhoea, salivation, incontinence
Other use “Nerve Gas”
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Nerve agents
Stable, easily dispersed, highly toxic, rapid effects through skin or via respiration
• Sarin
Sarin inhibits the acetylcholinesterase enzymes.
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NMJ transmission disorders- how it works, presentation, diagnosis and treatment
Lambert-Eaton syndrome
* Presynaptic –reduced ACh release
* Rare autoimmune response which inhibits Ca2+ channels and thereby reduces ACh release
Presentation:
* The mean age of onset ~ 60 years
* Characterized by fatigue, weakness in limb muscle groups, autonomic dysfunction, and abnormal reflexes
* Does not usually effect respiratory, facial or eye muscles
* Dry mouth
* Symptoms almost always precede detection of cancer - patients rarely complain of lung issues. About half patients have “small cell lung cancer”
Diagnosis:
Electromyography (EMG) – apply electrical impulses to nerves and measuring the electrical response of the muscle. Clinical and laboratory findings, chest x-ray for a possible lung malignancy, antibodies to calcium channels.
Treatment:
* Use of immunosuppressant's such as corticosteroids
* Amifampridine –drug which blocks K+ channel so action potential duration is increased, so more ACh released.
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Molecular mechanisms of muscle contraction
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• Muscle anatomy
– Macroscopic
– Microscopic
• Muscle contractions
– Molecular
– Movement
• Muscle disorders
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Types of muscles
* Pennate muscles-feather-like in the arrangement of their fascicles (fibre bundles): unipennate, bipennate, or multipennate
* Fusiform muscles-spindle-shaped
* Parallel muscles- fascicles lie parallel to the long axis of the muscle- Flat muscles with parallel fibres often have aponeuroses
* Convergent muscles have a broad attachment from which the fascicles converge to a single tendon
* Circular muscles surround a body opening or orifice, constricting it when contracted
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Differences between skeletal, cardiac and smooth muscle
Skeletal muscle: striated, multinucleated, voluntary, non-branching, attached to skeleton
Cardiac muscle: striated, single nucleus, involuntary, branched, heart muscle
Smooth muscle: non-striated, single nucleus, involuntary, tapered, forms walls of organs
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Sarcomere
Segment between two neighbouring Z-lines
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Z-line
The disc in between the I bands- appears as a series of dark lines
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I-band
The zone of thin filaments (not superimposed by thick filaments)
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A-band
Contains the entire length of a single thick filament
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H-zone
The zone of the thick filaments (not superimposed by the thin filaments)
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M-line
Formed of cross-connecting elements of the cytoskeleton
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What does titin do?
Titin (connectin) extends from the Z-line of the sarcomere, where it binds to the thick filament (myosin) system, to the M-band, where it is thought to interact with the thick filaments.
74
What does nebulin do?
Nebulin-hypothesised to extend along the thin filaments and the entire I-band.
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How does muscle contraction occur?
1. Action potential arrives neuromuscular junction
2. Ach released – binds to receptors so opens Na channels
3. Action potential sarcolemma and travels along T-tubules
4. Ca released sarcolemma binds to troponin complex region troponin
5. Troponin changes shape – tropomyosin moves so expose binding sites
6. Attachment – myosin head (+ ADP + Pi) binds actin
7. Power stroke – myosin head bends so pulls actin filaments -ADP + Pi released
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Cross-bridge theory
1. Myosin head attached to actin forming a cross bridge
2. Inorganic phosphate generated in the previous contraction cycle is released, initiating the power stroke. The myosin head pivots and bends as it pulls on actin, sliding it towards the M line. ADP is then released.
3. As the new ATP attaches to myosin head, the link weakens and the cross bridge detaches
4. As ATP splits into ADP and phosphate, the myosin head is energised
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Sliding filament model
* Action potential sent releases Ca
| * In muscle contraction – A band remains unchanged Z line shortens (distance changes)
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What is an isotonic contraction?
Cause the muscle to change length as it contracts and causes movement of a body parts
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Two types of isotonic contraction- concentric and eccentric
Concentric contractions are those which cause the muscle to shorten as it contracts.
Eccentric-opposite of concentric and occur when the muscle lengthens as it contracts
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Isometric Contractions
Isometric Contractions -occur when there is no change in the length of the contracting muscle
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Twitch
Twitch is the mechanical response of an individual muscle fibre, an individual motor unit, or a whole muscle to a single action potential.
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Motor unit
The motor unit consists of a motor neuron and all the muscle fibres it innervates.
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Phases of the Twitch
When a stimulus is applied and a fibre contracts the twitch can be divided into phases:
1. Latent period is the delay of a few milliseconds between an AP and the start of a contraction and reflects the time for excitation-contraction coupling.
2. Contraction phase starts at the end of the latent period and ends when the muscle tension peaks. During this time cytosolic calcium levels are increasing as released calcium exceeds uptake.
3. Relaxation phase is the time between peak tension and the end of the contraction when the tension returns to zero. During this time cytosolic calcium is decreasing as reuptake exceeds release.
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Slow twitch fibres- Type I
* Red in color due to high concentrations of myoglobin
* Resistant to fatigue
* Contains large amounts of mitochondria
* Contracts slowly
* Produces a low amount of power when contracted
* Used in aerobic activities such as long distance running
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Fast twitch A fibres- Type IIa
* Red in color due to high concentrations of myoglobin
* Resistant to fatigue (but not as much as Type I fibers)
* Contains large amounts of mitochondria
* Contracts relatively quickly
* Produces a moderate amount of power when contracted
* Used in long-term anaerobic activities such as swimming (activities lasting less than 30 minutes)
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Fast twitch B fibres-Type IIb
* White in color due to low myoglobin concentrations
* Fatigue very easily
* Contains low amounts of mitochondria
* Contracts very quickly
* Produces a high amount of power when contracted
* Used in short-term anaerobic activities such as sprinting and lifting heavy weights (activities lasting less than a minute)
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Force of muscle contraction (3 factors)- number of AP per second
* When the frequency of stimulation is so high that Ca++ levels rise to peak levels, summation results in the level of tension reaching a plateau called tetanus
* When the frequency of stimuli is high enough to cause tetanus but tension oscillates around an average level, the tetanus is called incomplete or unfused
* At greater frequencies of stimulus, levels of Ca++ peak and cause a maximum number of crossbridges to cycle
* At this point the tension plateau smoothes out and tetanus is called complete or fused
* When the muscle is at maximum sustained tension it is said to have reached maximum tetanic tension.
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Force of muscle contraction (3 factors)- Amount of overlap between thick and thin filaments
* When the muscle is at the optimum length the number of active cross bridges is the greatest
* When the muscle is stretched beyond this length the number of active cross bridges decreases because the overlap between the actin and myosin fibres decrease
* As the muscle becomes shorter than the optimum length the thin filaments at opposite ends of the sarcomere first begin to overlap one another and interfere with each other's movements
* This results in a slow decrease in tension as the sarcomeres get shorter. Then as the sarcomeres get shorter the thick filaments come into contact with the Z lines and the decrease in tension with decreasing length becomes even steeper
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Force of muscle contraction (3 factors)-
Number of motor units recruited
* To generate small forces only smaller motor units are stimulated
* When larger forces are needed larger motor units are recruited
* This enables fine movements to be controlled by the smaller increments of force generated by the smaller motor units. When greater force is required, the larger increments come from the larger motor units. The force of contraction increases as the larger motor units with increasing numbers of fibres are recruited.
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Muscle disorders: Injury or overuse, genetic, neurological, inflammation
Injury or overuse- Strains, cramps, tendinitis, cramps, sprains
Genetic- muscular dystrophy
Neurological- Parkinson’s disease, Myasthenia gravis, MS
Inflammation- Polymyalgia rheumatica, myositis
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Skeletal muscle
– Attached to bones
– Striated
– Multinucleated
– Responsible for locomotion, facial expressions, posture, respiratory movements, other types of body movement
– Voluntary in action; controlled by somatic motor neurons
– Non-branched
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Smooth muscle
– In walls of hollow organs, blood vessels, eye, glands, uterus, skin
– Non-striated
– Single nucleus
– Functions eg: propel urine, mix food in digestive tract, dilating/constricting pupils, regulating blood flow
– In some locations autorhythmic
– Controlled involuntarily by endocrine and autonomic nervous systems
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Cardiac muscle
– Unique to only the heart: major source of movement of blood
– Autorhythmic
– Controlled involuntarily by endocrine and autonomic nervous system
• Striated – like skeletal
• Branched
• Interconnected
• Cardiac smaller than skeletal muscle cells
• Rich in glycogen, myoglobin and mitochondria
• Found only in heart where it forms a thick layer called the myocardium
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Ultrastructure of cardiac muscle
* Each cell usually contains 1-2 nuclei
* Increased mitochondria
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Intercalated discs:
- specialized cell-cell contacts
- Cell membranes interlock
Two functions
- Mechanical coupling- desmosomes hold cells together
- Electrical coupling:
Gap junctions allow action potentials to spread quickly to adjoining cells
Fascia adherens actin anchoring sites
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Three types of cell junction make up an intercalated disc
Fascia adherens, desmosomes and gap junctions.
Desmosomes stop separation during contraction by binding intermediate filaments, joining the cells together.
Desmosomes are also known as macula adherens.
Gap junctions allow APs to spread between cardiac cells by permitting the passage of ions between cells, producing depolarization of the heart muscle.
Fascia adherens are anchoring sites for actin, and connect to the closest sarcomere.
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Gap Junction
• Some cells are autorhythmic
– Fibers spontaneously contract (sino atrial node-pacemaker cells)
• Electrically, cardiac muscle of the atria and of the ventricles behaves as single unit (Functional Syncitium)
• Bidirectional
• Under control of the ANS (involuntary) and Endocrine system (hormones)
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Gap junction two types of cells
- Contractile cells
- Myocytes contract the heart
- Do not initiate their own AP
- Autorhythmic cells
- Initiate APs
- No stable resting membrane potential; neural input not necessary to initiate an AP
- Pacemaker activity instead: slow depolarization, drift to threshold, then firing
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Cardiac Muscle Action Potential at different locations in the heart
Conduction of pacemaker potential from nodal tissue to adjacent contractile cells and beyond, through gap junctions in intercalated disks
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Wolff-Parkinson- White (WPW) syndrome
Caused by presence of abnormal electrical conduction pathway between the atria and the ventricles. Electrical signals travelling down this abnormal pathway may stimulate the ventricles to contract prematurely.
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The 5 Phases of the Ventricular Action Potential
Phase 0 -Cell depolarisation; greatly increased membrane permeability to Na+ ions, which rush in through fast channels, down conc. gradient, reversing cell polarity (fast current)
Phase 1 -Partial repolarisation; loss of Na+ conductance- Na ion channels close, & 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
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 -Resting potential the interval between action potentials when the ventricular muscles are at their stable resting membrane potential
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4 main classes of antiarrhythmics
- class I-sodium channel blockers -treat ventricular ectopics
- class II-beta blockers-slow conduction in the SA & AV nodes
- class III-potassium channel blockers- treat ventricular tachycardia & atrial fibrillation
- class IV-calcium channel blockers-slow conduction in the SA & AV nodes
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The Skeletal muscle Action Potential
Skeletal muscle AP:
• Short refractory period
• Long twitch
• Muscle can be re-stimulated i.e. during the muscle contraction allows summation of twitches
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Cardiac muscle AP
* Long refractory period as long as the muscle twitch
| * Can’t get summation- ventricles need time to fill
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Cardiac Excitation-Contraction Coupling
1. The AP invades the T-tubules
2. This opens voltage-gated L –type Ca2+ channels in the T-tubule membrane (there is an abundance of these channels, unlike the situation in skeletal muscle)
3. Ca2+ enters through these channels and this triggers further Ca2+ release from the adjacent sarcoplasmic reticulum:-amplifies Ca2+ ‘calcium-induced calcium release’
4. Ca2+ binds to troponin-C and contraction proceeds in the same way as in skeletal muscle
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Digoxin
- Inhibit Na/K ATPase pump
1. Increase in intracellular sodium levels.
2. Resulting in reversal of action of the sodium-calcium exchanger, which imports 3 Na ions in cell and 1 calcium ion out of cell.
3. Increase in Ca concentration is available to the contractile proteins. Increased calcium leads to increased storage in sarcoplasmic reticulum.
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SA node depolarization
Calcium influx (rather than sodium) for rising phase of the AP. Each depolarization creates one heartbeat.
• SA node-no stable resting membrane potential
• Pacemaker potential
– gradual depolarization- slow influx of Ca2+, reduced K+ permeability.
• AP
– occurs at threshold of -40 mV
– depolarizing phase
• Due to fast Ca2+ channels open, (Ca2+ in)
– repolarising phase
• K+ channels open, (K+ out)
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Autonomic (involuntary) system on pacemaker function- Ach and Noradrenaline
Acetylcholine (from parasympathetic nerves)
• Stimulate vagus nerve
• Decrease SA node rate
• Decrease heart rate
Noradrenaline (from sympathetic nerves)
• Increases rate of depolarisation of pacemaker cells of SA node
• Increase AP rate
• Increase heart rate
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Frank-Starling law of heart
* The resting length of cardiac muscle cells is set below its ‘optimal level’
* The degree of overlap between the thick and thin filaments in the ventricular muscle cells is less than optimal
* 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
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Smooth muscle- involuntary muscles- how they work
* Usually 2 sheets of closely opposed fibers
* Walls of all but smallest blood vessels & in walls of hollow organs (respiratory, digestive, urinary, reproductive tracts)
* Alternating contraction and relaxation of the 2 layers mixes substances in lumen of hollow organs = peristalsis
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Ultrastructure of Smooth Muscle
```
• Fibers smaller than skeletal muscle
• Spindle-shaped
• Central nucleus
• More actin than myosin
• No sarcomeres
– Thick and thin filaments not well organised (unlike skeletal muscle), thus no striations
• No T-tubules and the sarcoplasmic reticulum is poorly developed
• Caveolae: indentations in sarcolemma
– May act like T tubules
• Actin attached to dense bodies
```
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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
* Once phosphorylated generates tension 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
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Features of smooth muscle
* Maintain force over long periods of time (e.g. Sphincters)
* Cross bridge cycling is much slower- contraction of smooth muscle occurs more slowly and the duration of the contraction in response to a stimulus is long
* Reduced ATP consumption
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Single-unit
Single-unit (Unitary) smooth muscle are the most common. Gap junctions so act as a single unit.
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Cardiac muscle disorders- Dilated Cardiomyopathy- What it is, causes and symptoms
* 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)
```
Causes:
• Viral Infection
• Auto-Immune Disease
• Excessive alcohol consumption/exposure to toxic compounds
• Pregnancy
• Familial disease
```
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Symptoms:
• Shortness of breath
• Swelling of the ankles
• Tiredness
• Palpitations and Syncope
• Chest pain
```
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Cardiac muscle disorders- Hypertronic cardiomyopathy- What it is, causes and symptoms
* Thickening of muscle; may thicken in normal individuals as a result of high blood pressure or prolonged athletic training. More common in young adults
* HCM -thickening without obvious cause
* Normal alignment of muscle cells is absent myocardial disarray
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Symptoms:
• Shortness of breath
• Chest pain
• Palpitation
• Light-headedness and blackouts
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Causes:
• Genetic mutation, of important proteins for the contraction of the heart
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Cardiac muscle disorders- Leiomyoma (fibroids)- What it is, causes and symptoms
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Leiomyoma (fibroids)
• Benign growth
• Female reproductive tract
• Usually multiple
• More prevalent approaching menopause
• Heavy uterine bleeding &/or pain
• Cause unknown, associated factors include genetic factor
```
