Session 5 - The Action potential Flashcards
- Describe the properties of the action potential
- Explain the ionic basis of the action potential
- Explain how the ionic permeability of the membrane alters with time
- Describe some molecular properties of ion channels
- Explain how local anaesthetics have their effects
- Describe how conduction velocity can be measured
- Explain the local circuit theory of propagation
- Explain how conduction velocity is linked to fibre diameter
- Explain the implications of myelination for conduction
- Describe certain consequences of demyelination
Describe the properties of the action potential LO (5)
- Change in voltage across membrane
- Depends on ionic gradients and relative permeability of the membrane
- Only occurs if a threshold level is reached
- All or nothing
- Propagated without loss of amplitude
Draw and give th RMP for axons, skeletal muscle, SA node and cardiac ventricular muscle
- If the conductance (g) to any ion is increased the membrane potential (Vm) will ?
- The conductance of the membrane to a particular ion is dependent on ?
- move closer to the equilibrium potential for that ion
- the number of channels for the ion that are open.
Explain the ionic basis of the action potential
Explain how the ionic permeability of the membrane alters with time during an AP
Describe the Channel activity during an axonal action potential
What is the ARP and RRP?
ARP - nearly all Na+ channels are in the inactivated state (no AP)
RRP - Na+ channels are recovering from inactivation, the excitability returns towards normal as the number of channels in the inactivated state decreases (maybe AP)
After the Na+ channels are opened, how can they open again?
Generally require K+ to go from inactivated to closed. So a change in mp can cause them to open again.
Describe some molecular properties of ion channels LO
What is the structure for voltage gated Na+ channels
- 1 peptide
- inactivation particle -> acts as a ply
- 4th traansmembrane domain is has positive aa - change in mp = conformational change
- p region -> dictate what ions go through the channel
Describe some molecular properties of ion channels LO
What is the structure for voltage gated K+ channels
P = selectivity filter
4 subunits to make a functional potassium channel but only one subunit for a functional sodium channel
S4= Conformational change
Explain how local anaesthetics have their effects LO
Local anaesthetics such as procaine act mainly by ?
blocking Na+ channels.
Local anaesthetics block in the following order:
- small myelinated axons
- un-myelinated axons
- large myelinated axons
What is this image showing?
how the local anaesthetic/ blocker cna block Na+ channels more easily when it is open and remains there in the inactive state
Describe how conduction velocity can be measured LO
Speed AP has to travel from the point of stimulus to get to different regions
- take into account the distance
- take into account the time
- work out conduction velocity
Why are the conduction velocities different?
Explain the local circuit theory of propagation LO
Injection of current into an axon will cause the resulting charge to spread along the axon and cause an immediate local change in the membrane potential.
But how far does this change in the membrane potential spread ?
- Capacitance, C, is the?
- The membrane resistance depends on?
- ability to store charge. This is a property of the lipid bilayer
- the no. of ion channels open. The lower the resistance the more ion channels are open.
- Spread of local current depends on ?
- membrane resistance and capacitance
- High capacitance –
- High resistance –
- High capacitance – voltage changes more slowly in response to current injection
- High resistance – change in voltage spreads further along the axon
Function of:
- Aα –
- Aδ –
- B –
- C –
- Aα – sensory fibres from muscle spindles, motor neurones to skeletal muscle
2. Aδ – sensory fibres from pain and temperature receptors (sharp localized pain) - B – preganglionic neurones of autonomic nervous system
- C – sensory fibres from pain, temperature and itch receptors (diffuse pain)
What is this image showing?
- Local currents cause the propagation of the action potential (The first AP spreads the second AP is over threshold)
- the period after the AP is refractory thus an AP can only travel in one direction
Explain how conduction velocity is linked to fibre diameter LO
Wider diameter axons will conduct faster
Explain the implications of myelination for conduction LO
- What is myelin?
- What are Na+ channels concentrated in myelinated axons?
- Function of the myelin sheath
- Myelin is a sheath of tightly packed membrane
- Nodes of Ranvier
- Insulation
saltatory conduction
Inc conduction velocity
AP only at nodes of Ranvier
What is the effect of myelinated and unmyelinated axons of conduction velocity
Myelin sheath improves conduction by:
Describe certain consequences of demyelination LO
Disease states affecting conduction of the action potential
- Central Nervous System e.g.
- Peripheral Nervous System e.g.
These diseases result from ?
- • Multiple sclerosis – all CNS nerves (most common)
• Devic’s disease – optic and spinal cord nerves only - • Landry-Guillain-Barre syndrome
• Charcot-Marie-Tooth disease
breakdown or damage the myelin sheath
Explain why there is no or little conduction of an AP in demyelinating diseases
- local current spread depolarizes next node above threshold
- In regions of demyelinaion the density of the action current is reduced because of resistive and capacitive shunting.
Generation of the action potential (5)
• depolarization to threshold triggers the opening of many voltage-gated Na+ channels
• the influx of Na+ produces the rapid upstroke of the action potential (membrane
potential moves towards ENa)
• this depolarization causes inactivation of Na+ channels and opening of voltage-
gated K+ channels
• Na+ influx stops and the increased K+ efflux leads to repolarization (membrane
potential moves towards EK)
• relatively little ions move and the Na/K ATPase is NOT involved in action potential repolarization
Conduction of the action potential
- an action potential causes local current flow leading to an immediate depolarization of adjacent bits of the axon
- where this local depolarization reaches threshold an action potential is initiated
• the spread of this local change in the membrane potential is increased by a high
membrane resistance and low membrane capacitance – the longer this distance the faster the conduction
- myelinated axons have a high membrane resistance and low membrane capacitance
- at nodes of Ranvier, between the myelin sheaths, the axon is bare and the membrane has a high concentration of Na+ channels
- the action potential jumps from node to node – termed saltatory conduction, which is faster than that in unmeylinated axons
- damage to the myelin (e.g. in multiple sclerosis) can stop saltatory conduction
Electrical exitability - synaptic transmission and the neuromuscular junction
- Explain how action potentials open Ca2+ channels
- Describe some aspects of Ca2+ channel diversity and function
- Describe events underlying fast synaptic transmission
- Describe some properties of ligand gated ion channels
- Explain how neuromuscular blockers work
- Explain why myasthenia gravis causes weakness
The neuromuscular junction is ?
the synapse between a nerve and a skeletal muscle fibre.
What happens at the nerve terminal ?
Explain how action potentials open Ca2+ channels LO
- Increasing frequency of action potentials has what effect on Ca2+ entry?
- increases amount of nerve terminal Ca2+ entry
Describe some aspects of Ca2+ channel diversity and function LO
The structure of the α-subunit of voltage-gated Ca2+ channels is very similar to voltage-gated Na+ channels, how?
- 1 peptide = one functional subunit
Which calcium isoforms will we most commonly appreciate
L -type
Nifedipine -> less Ca2+ entry -> useful for high bp as less contraction of arteries
A pore forming subunit is necessary for a functional channel Other associated subunits fine-tune the properties and enable correct regulation of channel activity
Properties of Ca2+ channels
- How does activation of Voltage-gated Ca2+ channels differ from voltage gated Na+ channels?
- How does activation of Ca2+ channels differ from Na+ channels?
- Ca2+ channel inactivation is ?
- activate more slowly than voltage-gated Na+ channels
- Ca2+ channels activate and inactivate – but much more slowly than Na+ channels
- Ca2+-dependent
Transmitter release:
- Ca2+ entry through Ca2+ channels
- Ca2+ binds to synaptotagmin
- Vesicle brought close to membrane
- Snare complex make a fusion pore
- Transmitter released through this pore
Release of ACh activates nicotinic ACh receptor channels what ions can pass through this channel? Which ions significantly pass through?
How does the end-plate potential initiate a muscle action potential?
- ACh released binds to nAChR
- influx of Na+ causes depolarisation (moves to ENa)
- ACh degraded by ACh esterase
- Depolarisation results in activation of adjacent volatage gated Na+ channels
Explain how neuromuscular blockers work LO
Give 2 examples of Blockers of nicotinic ACh receptors
Explain how tubocurarine works
Can the effect of tubocurarine be overcome?
The block by d-TC can be overcome by increasing the concentration of ACh
Explain how succinylcholine works
Succinylcholine binds to nAChR results in depolarisation -> opens adjacent Na channels
continuous depo from nAChR doesn’t allow for reactivation of adjacent Na channels
Explain why myasthenia gravis causes weakness LO
Mayasthenia gravis
- What is it?
- Symptoms
- Explain the reasoning for the symptoms
- an autoimmune disease targeting nACh receptors.
- • Patients suffer profound weakness
• Weakness increases with exercise
- • Caused by antibodies directed against nAChR on postsynaptic membrane
of skeletal muscle
• Antibodies lead to loss of functional nAChR by complement mediated lysis and receptor degredation
• Endplate potentials are reduced in amplitude leading to muscle weakness
and fatigue
Summary of transmission at the neuromuscular junction:
• Action potential arrives at the motoneurone terminal where it opens voltage-gated Ca2+ channels.
- Ca2+ entry initiates exocytosis of vesicles containing ACh.
- ACh binds to nicotinic ACh receptors on the muscle end-plate, causes them to open and the flow of cations causes a depolarization called the end-plate potential.
- The end-plate potential depolarizes the adjacent muscle membrane and activates voltage-gated Na+ channels, thereby initiating an action potential in the muscle fibre which then contracts due to excitation-contraction coupling.
• nACh receptors can be blocked competitively by d-tubocurarine – this causes
paralysis.
• Drugs such as succinylcholine are known as depolarizing blockers and work by causing inactivation of the Na+ channels adjacent to the neuromuscular junction.
Other than nAChR what does ACh bind to? Which part of the NS is this seen?
mAChR = muscarinic ACh receptor
Nicotinic and muscarinic ACh receptors operate differently, why?
- nAChR produces a fast depolarization because it is a ligand gated ion channel
- mAChR produce a slower response because they are coupled to G- proteins which trigger a cascade of events in the cell.
