What is happening, and what is the charge of the membrane during the central region or focal depolarization of an axon?
Na+ influx in which there is a net positive charge on the inside of the membrane
What is happening, and what is the charge of the membrane during the behind region of an axon?
there is a net negative intracellular charge
axon has just experienced an influx of Na+ and is now experiencing and outward K+ efflux
What type of capacitative current is there during the forward and behind regions of the action potential?
outward depolarizing capacitative current since it is a capacitative current and since the redistribution of charge would result in membrane depolarization in the forward and behind regions.
What is a capacitative current?
no transfer of charges across the plasma membrane, only change of charge on the capacitor
What is happening, and what is the charge of the membrane during the forward region of an axon?
at resting potential and has a net negative intracellular charge
How do you define the direction of current in respect to the difference in charges between the behind, central, and forward regions?
the direction a positive charge would flow without crossing the membrane
What is the primary function of the current in an axon?
What kind of current is it?
To redistribute the charges on the inside and outside surfaces of the membrane
How does the outward depolarizing capacitative current across a membrane get set up?
it does not refer to the actual movement of ions across the plasma membrane, but to a change in the charge across the plasma membrance that is produced by the redistribution of charges occuring on the inside and outside surfaces
What do we consider to be the membrane capacitance and what does it do?
the membrane capacitance is the lipid bilayer
it separates and stores charge
What is the dominant current in the forward region?
the outward depolarizing capacitative current, which will depolarize the membrane in theis region to a voltage above threshold and will result in the opening of voltage gated fast Na+ channels
the region of inward Na+ current will therefore move in the forward direction
What is the dominant current in the central region?
inward ionic Na+ current through open voltage gated fast Na+ channels
Na+ will soon close by inactivation gates and delayed recifier K+ channels would open.
What is the dominant current in the behind region?
there are two currents that have opposing effects:
- outward depolarizing capacitative current
- outwward movement of K+ through the delayed rectifier K+ channels which makes the membrane potential more negative
the K+ current is the stronger of these two currents
the membrane continues to hyperpolarize and eventually goes back to resting potential
Where is the absolute refractory period?
in the behind region when the Na+ channels remain inactivated and no amount of depolarizing capacitative current could re-open them
it is said to be in the absolute refractory period, and the outward K+ current opposes the outward depolarizing capacitative current
a single action potential is conducted in the foward direction along the axon
What determines the rate of charge delivery to the forward region?
the value of the internal axoplasmic resistance (ri)
ri is determined by axonal diameter:
large diameter, low resistance, faster conductance
I=gv (current = conductance x membrane potential)
Explain the influence fiber diameter has on conduction velocity.
Large diameter fibers have lower internal axoplasmic resistances
Axons with lower axoplasmic resistances have faster rates of positive charge delivery (larger i ir) to the foward region
The forward region of axons with larger i ir's (larger rate of charge delivery) will reach threshold sooner than the foward region of axons with smaller rates of charge delivery because conductance is faster
Larger diameter fibers will conduct impulses more rapidly than small diameter fibers (have a faster conductance velocity)
What kinds of channels are concentrated at the internode?
How does the myelin sheath work in these areas?
delayed rectifier K+ channels are concentrated at the internode, where the capacitance is high and the membrance resistance is low
the myelin sheath separates charges on the plasma membrane, providing and additional barrier to the movement of ions between the axoplasm and the extracelluar space
this creates a higher effective membrane resistance in the internode than at the nodes of ranvier
this means that less resistive current can escape through the membrance in the internode and that more current will be available at the nodes
What is responsible for producing the internal resistive current from the central region to the forward region?
How is the magnitude of this internal resistive current measured?
The voltage across the membrance in the forward region, minus the voltage across the membrane in the central region (Vf - Vc)
The magnitude of this internal resistive current (dQ/dt) equals the rate of charge delivery to the foward region, and therefore determines the rate of acccumulation of charge across the membrance capacitance in the foward region
What kinds of channels are concentrated at the nodes of ranvier?
Na+ fast channels are concentrated here, where the capacitance is high and the membrane resistance is low
How does the myelin sheath at the internodal regions decrease the membrance capacitance?
The myelin sheath at internodal regions increases the distance between the oppositely charged dipoles on the inside and outside surfaces of the axon
This reduces the attractive force which is responsible for storing these charges on the membrane capacitance
Therefore, this reduces the amount of charge stored for a given transmembrane voltage (reduces the membrance capacitance)
As a result, the membrance capacitance in the internodal region is lower than at the nodal region
What is the capacitative current directly proportional to?
What does this mean?
How does this create saltatory conduction?
How does this explain the faster conduction velocities in myelinated axons?
The capacitative current is directly proportional to the membrane capacitance, meaning that the capacitative current in the internode is smaller than at the node
The capacitative current is concentrated at the nodes of ranvier, and the depolarizing outward capacitative current is foces at the node and jumps from one node to the next
This type of jumping conduction is called saltatory and is responsible for the faster conduction velocities in myelinated axons
What are three functional specializations that result in an increase in conduction velocity in myelinated axons?
a lower membrance capacitance in the internodes, which effectively focuses capacitative current at the nodes
a higher membrane resistance in the internodes that reduces transmembrane "leak" and therfore maximizes the movement of charge to the next node
a lower internal resistance which maximizes the rate of charge delivery from one node to the next
What is the primary function of myelination?
To focus capacitative current at the nodes
How are channels distributed in myelinated axons?
How does the lack of delayed rectifier K+ channels at the nodes of Ranvier affect the falling phase of the action potential?
Na+ channels are concentrated at the nodes, and K+ channels are concentrated at the internodes
There are no voltage gated Na+ channels at the internodes and no voltage gated K+ channels at the nodes
Since there is a lack of delayed rectifier K+ channels at the nodes, the falling phase of the action potential at the nodes is produced by ion movement through one or more classes of "leakage" channels which are not voltage gated
How are channels distributed in unmyelinated axons?
fast Na+ channels and delayed rectifier K+ channels are interspersed along the axonal membrane
What is the compound action potential and how is it used?
Since nerves contain several myelinated and unmyelinated axons of varying diameters, the recordings from stimulated nerves results in compound action potentials that represent the summed activity of all the activated axons within the nerve bundle
The compound action potential is used to measure the conduction velocity for various classses of axons
What would you expect to see if a nerve contained several populations of axons that conduced at different velocities?
What would our ability to differentiate these waves depend on?
If a nerve contained several populations of axons that conduced at different velocities, then the compound action potential would contain several individual waves corresponding to each population
Our ability to differentiate these waves would depend on the distance between the recording electrode and the site on the membrane where the action potentials were initated
At close distances, we would not be able to differentiate populations that differed only slightly in conduction velocity, while at larger distances, we would be able to detect individual waves marking the arrival of these populations
What are the two classifications of axons that differ according to their average conduction velocities?
Sensory classification: axons that convey sensory information
General classification: applies to all axons
What are two functional consequences of demyelination that lead to conduction block?
What does this do to conduction velocity?
Increased capacitance at the internodes leads to increased capacitative current at the internode, thus diverting current from the node of Ranvier where the fast Na+ channels are concentrated
Increased capacitative current at the internode activates delayed rectifier K+ channels that produce an outward, hyperpolarizing ionic current
Conduction velocity will still reach threshold, it will just take longer
What happens in more severe demyelination?
What is conduction block?
In more severe demyelination, there is an even greater outward ionic current at the internodes (greater activation of K+ channels), diverting even more current from the nodes of ranvier
This can result in a conduction block, or failure to reach threshold
What effect do demyelinating neuropathies have on compound action potentials?
What is this effect called?
demyelination causes broadening in compound action potentials, named temporal dispersion
temporal dispersion decreases conduction velocity
Explain frequency dependent conduction block in demyelinated axons.
Low frequency stimulation gets full conduction and the same amplitude as normal. All axons (myelinated and demyelinated) are conducting and there is no block.
High frequency stimulation causes as loss of conduction in axons with demyelinating disease, but not with normal myelinated axons
What are the 6 electrophysiological signs of demyelinating neuropathy?
Decreased conduction velocity that is not focal and that is not produced by physical injury (eg. compression)
Broadened compound action potential indicating temporal dispersion of action potentials in affected nerves
Conduction block: frequency-dependent or total
Ectopic impulses: impulses fired in wrong place
Increased mechanosensitivity to pressure: membrane more naked and sensitive to pressure
"Cross-talk" between neighboring demyelinated axons: action potential on one axon can produce action potential on another = chaos!
What happens when action potentials propagate from a normally myelinated region into a demyelinated area?
The axial action current that was generated at the last healthy node is distributed across a long region of bare or partially myelinated axonal membrane, with its decreased resistivity and increased capacitance.
Thus, the current density at the two affected nodes is greatly reduced.