Week 4 - Action Potential and Conduction of the Nerve Impulse Flashcards
What are action potentials?
A change in voltage across the membrane
- Only occur if the threshold value is reached
- Propagated without loss of amplitude
- All or nothing
- They are generated by an increase in permeability to Na+, which brings the membrane close to the Na+ equilibrium potential (Ena)
What do action potentials depend on?
- Ionic gradients (movement of Na+ and K+)
- Relative permeability
Which ion channels are used in nervous transmission?
Voltage-gated Na+ and K+ channels
- Depolarisation causes them to open
- Once a certain membrane potential (threshold potential) is reached a positive feedback occurs as Na+ channels begin to open
What is the ‘all or none’ characteristic of the action potential?
- If the membrane depolarisation reaches the threshold value, then an action potential will occur
- If it does not reach the threshold value then no action potential will be produced
What happens after depolarisation of the membrane?
- K+ channels are opened
- K+ efflux
- Na+ channels are inactivated
- Na+ influx is stopped
What does ‘inactivation of a Na+ channel’ mean?
There is an inactivation molecule
There is an outer gate
- Shut at resting potential
- Opens as the membrane potential depolarises, allowing Na+ through
- It closes during inactivation
There is an inner gate
- Open at resting potential
- When the membrane depolarises, Na+ can pass through it
- As the membrane becomes more positive, the inner gate gradually shuts
- It shuts completely during inactivation
What happens if the conductance to an ion is increased?
The membrane potential will move closer to the equilibrium potential for that ion
- The conductance of the membrane to a particular ion is dependent on the number of channels that are open for the ion
What is the absolute refractory period?
When nearly all the Na+ channels are in the inactivated state, so the membrane is unexcitable
What is the relative refractory period?
Na+ channels are recovering from inactivation
- The excitability returns towards normal as the number of inactivated channels decreases
How are Na+ and Ca2+ channels similar?
- Main pore forming subunit is 1 peptide consisting of 4 homologous repeats
- Each repeat consists of 6 transmembrane spanning domains
- 1 of these domains is able to sense the voltage field across the membrane
Describe voltage-gated K+ channels
- Similar in structure to Na+ and Ca2+ channels, except each repeat is in fact a separate subunit
- A functional channel requires 4 subunits
- Each subunit still has 6 transmembrane domains, 1 of which is voltage sensitive
How do local anaesthetics act?
By binding to and blocking Na+ channels
- This stops generation of an action potential
- They only affect open Na+ channels
What do local anaesthetics block?
In the following order:
- Small myelinated axons
- Un-myelinated axons
- Large myelinated axons
What is accommodation?
The longer the stimulus, the larger the depolarisation necessary to initiate an action potential
- The threshold value is reached, but over a very long time and very gradually
- The Na+ channels have open, but by the time the threshold value has been reached they have been inactivated
- Hence no action potential is fired
How can you do extracellular recording of electrical activity?
Electrical stimulation
- Occurs under a cathode (excitability will be reduced under an anode)
- This can be used to stimulate an axon or group of axons to threshold, thus initiating an action potential
Recording
- Record changes in potential between the stimulating (cathode) and recording (anode) electrodes along an axon, and the time gap between the stimulus and action potential
- Conduction velocity can be calculated (distance/time)
How is an action potential conducted along an axon?
A change in membrane potential in 1 part can spread to adjacent areas of the axon
- This occurs because of local current spread (local circuit theory of propagation)
- When local current spread causes depolarisation of part of the axon to threshold, then an action potential is initiated in that location
How is the conduction velocity affected?
Determined by how far along the axon these local currents can spread
- The further it spreads, the faster the conduction velocity of the axon will be
- Affected by properties of the axon
- Myelination
What properties of the axon lead to a high conduction velocity?
- A high membrane resistance
- A low membrane capacitance
- A large axon diameter (leads to a low cytoplasmic resistance)
What is capacitance?
The ability to store charge
- A high capacitance takes more current to charge
What does membrane resistance depend on?
The number of ion channels open
- The lower the resistance, the more ion channels are open
Explain the local circuit theory of propagation
- The depolarisation of a small region of membrane produces transmembrane currents in neighbouring regions
- As Na+ channels are voltage-gated, this opens more channels, causing the propagation of the action potential
- These local currents cause the action potential to propagate down the axon
- It is faster than action potential spread over the axonal membrane
How is conduction velocity linked to fibre diameter?
- Myelinated: velocity is proportional to diameter
- Unmyelinated: velocity is proportional to the square root of the diameter
How does myelination affect conduction velocity?
Myelin reduces the capacitance and increases the resistance of the axonal membrane
- This increases conduction velocity
What is saltatory conduction?
Occurs in myelinated nerve fibres
- Due to the reduced capacitance in the internodal region, the local axonal current (induced by an action potential at a node of Ranvier) spreads further down the axon to depolarise the next node without firing an action potential in the internodal region
- Nerve conduction occurs in a ‘jumping’ manner down the nerve
- This greatly increases conduction velocity
What happens in regions of demyelination?
The density of the action potential current is reduced
- This is because of resistive and capacitive shunting
- Threshold value cannot be reached, so no action potentials are produced
What diseases are there in the PNS that involve areas of some axons losing their myelin sheath?
- Laundry-Guillain-Barre Syndrome
- Charcot-Marie-Tooth disease
What diseases are there in the CNS that involve areas of some axons losing their myelin sheath?
- Multiple sclerosis (all CNS nerves)
- Devic’s disease (optic and spinal cord nerves only)
Describe multiple sclerosis
Myelin is destroyed in certain areas of the CNS
- This can have dramatic effects on the ability of previously myelinated axons to conduct action potentials properly
- Can lead to decreased conduction velocity, complete block or cases where only some action potentials are transmitted