Describe the properties of voltage-gated ion channels
q
Describe the general features of electrically excitable membranes
q
Describe the permeability changes associated with the action potential
Permeability to Na increases as sodium channels open when the membrane depolarises
What factors can affect conduction velocity in nerves?
The axon diameter
Myelination
Resistance
Capacitance
How do ligand-gated ion channels work?
x
What steps are involved in the neurotransmission at the mammalian neuromuscular junction?
q
Why is the control of intracellular Ca2+ concentration so important?
q
What is saltatory conduction?
The propagation of action potentials along myelinated axons from one Node of Ranvier to the next node. This increases the conduction velocity of action potentials
How does conduction work in unmyelinated nerves?
The local current theory:
The first action potential occurs at the stimulus and propagates along the neuron by altering the membrane potential around the channels, when it reaches threshold the nearby channels will open and the action potential propagation continues
How does conduction work in myelinated nerves?
It works by jumping between nodes of Ranvier, where the action potential occurs and allowing the conduction to occur with greater conduction velocity, skipping the internodal region
How do the ionic movements through ion channels occur in myelinated nerve fibres?
They occur through Na+ channels at the Nodes of Ranvier where there is a high density of Na+ channels
How does myelination occur?
It is formed by cells:
Schwann cells in peripheral axons
Oligodendrocytes in CNS axons
When during development does myelination occur?
q
What conditions cause demyelination to occur?
Multiple Sclerosis (all CNA nerves) Devic's disease (optic and spinal cord nerves)
What are the consequences of demyelination?
Poorer transition of the local circuit which therefore fails to reach threshold and the signal is not propagated along the axon
Density of the action current is reduced because of resistive and capacitive shunting
Some myelinated nerve fibres are able to regenerate from the central end if cut. Does this occur in the PNS or the CNS? What is the rate of such regeneration?
This regeneration occurs in the PNS, not in the CNS
What is known of the distribution of ion channels in the myelinated nerve fibres?
The ion channels are found at the nodes of Ranvier in high densities and very few are found in the internodal region
Describe the properties of the action potential
- Change in voltage across the membrane
- Depends on ionic gradients and relative permeability
- Only occurs if threshold is reached
- It is all or nothing
- It is propagation without loss of amplitude
Describe the ionic basis of the action potential and the associated changes in membrane ionic permeability
It is generated by an increase in permeability to Na+, bringing the membrane close to the Na+ equilibrium potential which re
What is the basis of the all-or-nothing law?
That the depolarisation of the membrane needs to reach a threshold level in order to generate an action potential, once over the threshold the same action potential is generated despite the strength of the signal
What is refractoriness?
The idea that behind the action potential, the sodium channels are still recovering and are inactive, yet the K+ channels are activated. There is a refractory period where no action potential can be generated in the area that has just been activated
What are the key molecular properties of ion channels?
q
Outline the action of local anasthetics
Work by blocking Na+ channels and thereofore blocking action potentials
What is the basis of extracellular recording
Voltage-clamp
Electrical stimulation under a cathode (-), excitability can be reduced under an anode (+). Which can be used to stimulate an axon or group of axons to threshold, thus initiating an action potential
How are axons raised to threshold?
Through depolarisation of the membrane that occurs as a result of Na+ channels opening and allowing Na+ into the cell, the potential gets closer to Ena and if depolarised past threshold potential will fire an action potential
How is conduction velocity linked to fibre diameter?
The greater the axon diameter, the greater the conduction velocity
True or false: A nerve fibre comprises several axons with different diameters
True
What is the local current theory?
Injection of current into an axon results in a passive and almost instantaneous depolarisation of the neighbouring section of the axon (Immediate local change in membrane potential) . This gets less the further it gets from the injection site
Most local anaesthetics are weak _____. They cross the membrane in their ________ form.
Bases
Unionised
Local anaesthetics block Na+ channels easier when they channel is open or closed?
Open
Do local anaesthetics have a higher affinity to the inactivated or activated state of the Na+ channel?
Inactivated
Do local anaesthetics have a higher affinity to the inactivated or activated state of the Na+ channel?
Inactivated
How do you work out conduction velocity of axons in a nerve fibre?
Conduction velocity= distance/time
What is capacitance?
The ability to store charge
The membrane resistance depends on the number of ion channels open. The lower the resistance the what?
The more ion channels open
The higher the resistance the what?
Further the voltage spreads along the axon
Spread of local current depends on what two things?
Membrane resistance
Capacitance
Local currents cause the propagation of what?
The action potential
Are there many ion channels underneath the myelin sheath?
Where are they located?
No, very few
The Nodes of Ranvier
Why does the myelin sheath increase the conduction velocity?
Increases resistance and insulates the membrane causing the local circuit currents to depolarize the next node
In myelinated neurones where does the action potential occur?
Only at the Nodes of Ranvier
What does myelin do in relation to the capacitance and the resistance?
It reduced capacitance and increases resistance
DIRECTLY proportional to fibre diameter in myelinated or unmyelinated neurones?
Myelinated
In unmyelinated it is proportional to the squareroot of the diameter
Myelin sheath improves conduction by what four things?
Large increase in membrane resistance
Large decrease in membrane capacitance
Increase in the length constant
Slight decrease in time constant
How many subunits are needed to combine to make a function potassium channel?
4
How many subunits are needed to make a function sodium channel?
One
