Action Potentials

Question 0

How can the mechanism of AP generation be investigated?

Answer 0

• voltage-clamping: controls the membrane potential so that the ionic currents can be measured (prevents change in membrane voltage in response to membrane current)
• different ionic concentrations: allows the contribution of various ions to be assessed
• patch-clamping: enables currents flowing through individual ion channels to be measured

Question 1

What are some important features of action potentials?

Answer 1

• change in voltage across membrane
• depends on ionic gradients and relative permeability of the membrane
• only occurs if threshold is reached (all or nothing)
• propagated without loss of amplitude

Question 2

Outline the different stages of an action potential.

Answer 2

1. Initial depolarisation
2. Threshold reached: Na+ channels open & K+ channels begin to open
3. Upstroke (depolarisation) until Na+ channels are inactivated (absolute refractory period)
4. K+ channels remain open causing downstroke (repolarisation)
5. Na+ channels begin to reactivate (relative refractory period) but cell is hyperpolarised (overshoot)
6. K+ channels close and more Na+ channels are reactivated - returns to resting membrane potential

Question 3

What is the significance of the absolute refractory period?

Answer 3

Prevents AP going backwards (directionality in impulse propagation)

Prevents re-entrant excitation

note: stronger stimulus needed to generate an AP during this period (effectively higher threshold)

Question 4

Define accomodation. How does this work?

Answer 4

Ability of nerve tissue to adjust to a constant source and intensity of stimulation so that some change in either intensity or duration is necessary to elicit a response.

Longer the stimulus, larger the depolarisation necessary to initiate an AP (threshold becomes higher)

Slowly increasing stimulus -> threshold potential becomes high enough that the AP will no longer be generated although the original threshold has been surpassed

Question 5

What are some examples of CNS demyelinating diseases?

Answer 5

Devic’s disease (neuromyelitis optica): decreased visual activity, muscle weakness, loss of bowel control

Multiple sclerosis (inflammatory demyelination of all CNS nerves):

• optic neuritis = mild fogging, pain on eye movements
• brainstem demyelination = vertigo, facial numbness/weakness, dysphagia (difficulty swallowing), dysarthia (unclear pronunciation)
• spinal cord lesions = difficulty walking, limb numbness, “electric shock” sensation radiating down trunk and limbs on neck flexion (Lhermitte’s phenomenon)

Treatment: 4-aminopyridine (increases length constant, therefore potential can travel further before it falls below threshold)

Question 6

What are some examples of PNS demyelinating diseases?

Answer 6

Landry-Guillain-Barré syndrome: numbness and weakness in limbs which develops after a respiratory or GI infection

Charcot-Marie-Tooth disease: progressive weakness and wasting of muscle in legs

Question 7

How can APs be recorded extracellularly, and how can this be used to diagnose demyelination?

Answer 7

Electrodes used to raise the membrane potential to threshold in order to generate an AP

Record changes in potential between the stimulating cathode and recording anodl

Diphasic recording is normal, monophasic recording indicates anode is in a damaged region of the neurone

Question 8

How do membrane resistance and capacitance affect conduction velocity, and how are these values affected in myelinated neurones compared to unmyelinated neurones?

Answer 8

Membrane resistance depends on no. of ion channels open

Capacitance (ability to store charge) depends on distance between intracellular and extracellular compartments

Myelinated: high Rm (Na+ channels only found at Nodes of Ranvier)
low Cm (increased distance between i and o) 
= increased conduction velocity

Question 9

Define saltatory conduction.

Answer 9

AP “jumps” from node to node, allowing a much faster conduction velocity as APs are only generated at the nodes

Question 10

When does myelination occur during development?

Answer 10

14th week of foetal development -> adolescence

Question 11

What is the effect of conduction of demyelination of a nerve fibre immediately after and after a long period of recovery?

Answer 11

Immediately after: conduction failure, increased capacitance and current leak prevents channels from being raised to threshold

Recovery period: slower conduction velocity due to redistribution of channels (effectively becomes unmyelinated)