6-8 Flashcards
What is an action potential?
A rapid, reversible change in membrane potential consisting of a depolarisation followed by a repolarisation
Excitable cells
Muscle cells
neurones
why use squid giant axons?
up to 1mm in diameter so hard to damage
What is a nerve cells resting potential?
-70mV
what are the phases of an action potential?
x 4
Rising phase
Repolarising phase
Hyper-polarisation
After hyper-polarisation
What happens in the rising phase of an AP?
-the hodgekin cycle
Based on an increasing membrane permeability to Na+
- initial depolarisation above threshold causes some voltage gated Na+ channels to open
- then Na+ enters axon down electrochemical gradient
- further depolarisation towards E(Na)
- causing more VG channels to open and cycle keeps going
- Positive feedback
What is an overshoot?
The membrane potential rises above 0mV and goes towards E(Na) and this shows that the axon doesn’t just become permeable to everything
What happens in the repolarising phase?
- Na+ permeability falls as as the channels in-activate
- at a slight delay from the Na VG, the VG potassium channels open and so increase permeability to K+
What causes hyper-polarisation?
- the Na+ and now closed but the K+ ones stay open for a few milliseconds later causing more K+ to move in causing more negative than resting potential
After hyper-polarisation?
The VG K+ channels close and the permeabilities of Na+ and K+ return to normal and therefore so does membrane potential
What do voltage-gated cation channels look like?
- 4 homologous polypeptide domains that form a pore between them
- Each domain made of 6 α-helices segments
DIAGRAM
What are the three key characteristics of V-G cation channels?
- Selectivity
- Voltage sensitivity
- Inactivation
How are channels selective?
x 2 ways
- pore loops connecting segments 5 and 6 of each domain are the walls of the aqueous pore
- negatively charged amino acids found near both entrances repel anions
- now size, smaller channels for Na+ stop K+ which is too big
- K+ use selectivity filter of four carbonyl oxygen atoms to form bonds with K+ and replace water of hydration
- Na+ cannot form all 4 bonds and so still hydrated is too big to pass through
- snug-fit model
How are channels voltage selective?
segment 4 of each domain has positively charged amino acids
- these move towards exterior and so outwards when membrane depolarises as ore negative on outside
How do channels go through inactivation?
Most VG inactivate after being open for a period of time
- exact mechanisms differ
- Cue for inactivation is actually the original depolarisation but the process takes longer
Na vs K channels?
2 differences apart from ion
- Na+ channels open more quickly in response to depolarisation that K+
- Na+ channels inactivate more rapidly too (1-2 msec)
How is the behaviour of sodium channels stochastic?
Only a certain probability of a given channel being closed, open or inactive based on membrane potential and immediate history
- still random
At what point is the activation threshold?
Where Na+ entry exceeds K+ loss
What is the ARP? the absolute refractory period?
the time-period following the beginning of an AP when a second AP cannot be generated no matter how large the stimulus as there are too many inactive channels. (Na+)
What is the RRP? The relative refractory period?
The time-period where a second AP can only be elicited with a stimulus of greater amplitude than normal.
How does an action potential propagate?
- Na+ come into axon during AP and the positive charge (not the actual ions) will spread in both directions down potential gradient.
- in forwards direction then cause depolarisation as push ions away from outside of axon to make inside negative
- Cause a local circuit
- if backwards can’t cause depolarisation as in ARP
What is Edgar Adrian’s All-or-Nothing idea?
As long as the stimulus (original) goes over threshold then AP occurs, if it doesn’t then no AP. So different magnitude stimuli cause same AP provided over threshold
What is a myelin sheath
layer of specialised cell membranes wrapped several hundred times around nerve axon
- high resistance and low capacitance
Where does myelin come from
In peripheral nervous system it is Schwann Cells but CNA it is oligodendrocytes
What are the sections of myelin called?
The myelinated regions are internodes and the breaks are the Nodes of Ranvier (this is where all the sodium channels are)
Why does myelin work?
Causes saltatory conduction which is where the local currents are elongated. Makes transmission quicker
- increases length constant λ
How do the two adaptations for increased speed of AP work?
picture
How does temperature affect transmission?
Higher temperatures cause faster transmission—>kinetics
How does making axons wider work?
Reduce resistance and so AP increase speed
Resistances present in nerves
- Re = external resistance of extracellular fluid
- Ra = axonal resistance = inversely proportional to axon’s cross sectional are
- Rm = membrane resistance for unit length of axon ( inverse proportion to membrane area and density of background ion channels)
What is the length constant?
The distance over which the voltage change caused by the sustained injection of current at position x=0 decays to 1/e (37%) of original value.
Why does the voltage change decrease?
leakage of current due to resistance and capacitance.
- so make less leaky or axon wider.
What is the decay of the voltage change?
Vx = V0 * (e*(-x/λ))
What is the length constant equal to?
λ = sqrt (Rm/Ra)
What is τ (time constant)
The time it takes for the membrane potential to rise from baseline to 63% (1-1/e) of its final (when x=λ)
What is τ equal to
Vt = Vinfinity (1-(e*(-t/τ)))
where τ = RmCm
How do we increase transmission in terms of λ and τ
increase λ and decrease τ
What is a synapse?
A specialised region of communication between two cells-> one needs to be an excitable cell
What is a gap junction?
An electrical synapse where ionic current can pass directly between two cells. Cells shared cytoplasm.
- like between muscle cells
Which is faster? Chemical or electrical synapses?
Electrical. Chemical have a synaptic delay of 0.5 to 2 ms
What is the neuromuscular junction?
The point where and α motor neurone with it’s bod in the ventral horn of the spinal cord
- innervates skeletal muscle
What is a muscle fibre?
A single muscle cell
What is a motor unit?
Where a group of fibres is innervated by same axon and will act together
What is another name for a NMJ (neuromuscular junction)?
Moto end-plates
What is the neurotransmitter in NMJs
acetylcholine (ACh)
Diagram of NMJ
Picture
How wide is the synaptic cleft?
50nm
What are junctional folds?
Folds in the post-synaptic membrane of muscle cell—>increase surface area
How is the ACh released into synaptic cleft?
- AP reaches terminal bouton
- Depolarisation causes opening of VG calcium channels on pre-synaptic membrane
- These close to active zones fo calcium into cell and then interacts with synaptotagmin (calcium sensor)
- Synaptotagmin promotes interaction between t-SNARE and v-SNARE to cause exocytosis of ACh (roughly 100-300 vesicles)
How does ACh cause AP in muscle cell?
- post-synaptic membrane has high density of NAChR (nicotinic acetylcholine receptors)
- One ACh molecule binds to each α-subunit to open channel
- both Na+ K+ can pass (but Na+ higher rate as greater gradient)
- cause depolarisation of muscle cell membrane
Structure of NAChR
ligand-gated ion channel
- in adult mammals it is a pentameric α2βδε structure (subscript 2)
- opened when ACh molecule bind to each of α subunits
2 Examples of toxins can affect the NMJ and how they work
- α-latrotoxin-from black widow spider
- makes membrane unusually permeable to Ca2+ and so over stimulates - Tubocurarine
- block NAChR
What are end-plate potentials?
caused by opening of NAChR leads to depolarisation of post-synaptic membrane at about 20-40mV in amplitude and only local
- it stimulates VG sodium channels so only AP if this over threshold
- looks like small hump before depolarisation near NMJ
What feature of normal AP do skeletal muscle APs not have?
no hyperpolarisation
what are miniature end-plate potentials
around 0.4mV when one vesicle released
- small depolarisation
- in discrete intervals
How to stop response at NMJ
Acetylcholinesterase
- breaks ACh into acetate and choline
- acetate diffuse into cells
- choline cannot be synthesised by motor nerve terminal so actively transported back across pre-synaptic membrane
- made back into ACh using acetate from acetyl coenzyme A
- new vesicles from endocytosis
- Ca2+ actively pumped out of cell
What is an Excitatory post-synaptic potential?
Small depolarisations of the dendrites that increase the probability that the cell will come to threshold and fire and AP
- often glutamate as transmitter
- increase Na+ entry
What is an inhibitory post-synaptic potentials
decrease the probability that the cell experiencing them comes to threshold
- Ofter GABA (brain) or glycine (spinal cord) as transmitter
- usually increase Cl- permeability
- Dont know how decreases chance of getting to threshold
Roughly how many synapses can a brain cell have
100,000
Where is the AP initiated?
axon initial segment which has a high density of VG sodium channels
- located just after axon hillock
How to increase depolarisation
Temporal or spacial summation
What does myogenic mean
The type of action potential generated by myocytes (muscle cells)
What is the pacemaker of the heart
SAN- Sino-atrial node
What is the funny current in myocytes?
The point when Na+ enters—> which is after repolarisation
How are AP made in myocytes
funny current causes Ca2+ entry through channels
- causes pacemaker potential and then causes AP when threshold
- AP in SAN cells based on Ca2+ entering through L-type VG channels
- spike is slower and much longer than neuronal AP
- repolarises when calcium channels inactivate and K+ leaves cell through VG delayed rectifier
Autonomic nervous system controls slope of pacemaker potential and so controls rater—> what does it not control
The initiation
What fibres in the spinal cord make up the peripheral nervous system?
—questionable
The spinal nerves and cranial nerve
What is the structure of spinal nerves?
all have a dorsal root, through which sensory axons enter the cord
- and a ventral root through which the motor axons leave
What are cranial and spinal nerves split into?
Efferent fibres (leave CNS) Afferent fibres (sensory)
What two roles do efferent fibres have?
- somatic motor system-> to skeletal muscle
2. Autonomic nervous system (to smooth muscle, cardiac muscle and glands)
Where do sensory nerve fibres have their cell bodies?
the dorsal root ganglia
- the axons go on to synapse with grey matter of spinal cord
what types of motor neurones supply skeletal muscle?
α motor neurones
What happens in a monosynaptic reflex arc?
- sensory and somatic motor fibres are directly coupled within the spinal cord
Where are the cell bodies of α motor neurones located? And where do their axons leave?
the ventral horn of the spinal cord
- axons leave via the ventral root and go directly to skeletal muscle
few skeletal muscles are involved in homeostasis. Give two examples
- Ventilation - involved in control of blood gas concentrations and pH
- use diaphragm and chest-wall muscles - Shivering - body temp control
- mediated by most skeletal muscles
How is smooth muscle innervated?
The autonomic nervous system
What three divisions make up the autonomic nervous system?
- sympathetic
- parasympathetic
- enteric
- both 1 and 2 are completely efferent fibres
What is the structure of the neurones in the parasympathetic and sympathetic pathways
same
- pre-ganglionic is usually myelinated and has cell body in CNA
- axon out of CNS to autonomic ganglion
- there is has cholinergic synapse with a number of post-ganglionic neurones
- cell bodies of these post are in ganglion and axons, usually unmyelinated go to innervate organ in question
- pre-ganglionic is usually myelinated and has cell body in CNA
What is the intermediolateral column?
where sympathetic nerve fibres have their cell bodies and then axon to sympathetic chain ganglia
- pre nerves are short and post are long-go to organs
What is the neurotransmitter of the SNS?
ACh which works of NAChR which is different from the NAChR in the NMJ in pre to post neurone
- at organ it releases noradrenaline
(often co-transmitted with neuropeptide Y or ATP)
What are chromaffin cells
cells in the adrenal medulla that release adrenaline
- when ach from preganglionic nerve of SNS
What are adrenergic receptors?
the g-coupled receptors that adrenaline and noradrenaline work on
- 2 classes
α and β
both activate both but noradrenaline stimulates α1 and β1 more than adrenaline
- same with 2 for adrenaline
What are β-receptors of adrenoceptors coupled with?
Excitory g-proteins which release cAMP as secondary messenger in cell as activate adenylyl cyclase
What are the α-receptors?
α2) coupled with inhibitory g-proteins to stop cAMP
α1) works to activate inositol phospholipid pathway via another g-protein
Are the PNS and SNS always opposite?
NO
- salivary glands work together
SNS=enzyme secretion
PNS=Liquid secretion
PNS nerves
pre = emerge from brain and carried within cranial nerves to target organs
- like vagus nerve (which is a mixed nerve)
-
Autonomic control of the heart
Increased - adrenaline and noradrenaline- SNS
decreased by ACh form PNS
- at rest subject to tonic parasympathetic stimulation (PNS)
- from vagus
How is heart rate increased?
β1 receptors on SAN cells respond to catecholamines-activate GCPR so increased cAMP
- opening of Na+ and Ca2+
- speed up depolarisation rate
- shorten pacemaker potential
What is the pacemaker potential?
slow, positive increase in voltage across the cell’s membrane (the membrane potential) that occurs between the end of one action potential and the beginning of the next action potential.
How slow heart down
Vagal ACh works of muscarinic receptors-GCPRs in SAN
- α-subunit inhibits adenylyl cyclase so reduce cAMP (so longer pacemaker potential)
- also βγ subunit opens K+ channels directly and hyperpolarises cell to -70mV rather than -60mV so longer to get to threshold
SNS on blood vessels
- noradrenergic fibres activate α subunits and maintain basal level of vasoconstriction=sympathetic tone
- changing tone can constrict or dilate vessel
- in skeletal muscle via β2 causes vasodilation (adrenaline at normal levels)
How can PNS affect blood flow?
Only in some areas like salivary glands
- very little influence of total peripheral resistance, unlike SNS
Fight or flight response
x 7
- heart rate increases
- exercising muscle arterioles dilate and others constrict
- Bronchioles dilate
- Glucose mobilised
- Gastrointestinal activity put on hold
- Pupils dilate
- Hair stands on end
How to end autonomic effects
- most noradrenaline from SNS is taken back via presynaptic membrane transporter (uptake 1 mechanism)
- Circulating adrenaline taken up into many different tissues (by uptake 2 transporters) enzymatically degraded in the cells
- end products secreted in urine (1-3 min half life) - ACh rapidly broken down by acetylcholinesterase in synaptic cleft
