Question

1. Multiple Sclerosis (MS)

(a) Provide an understanding of how the physiological process axon demyelination relates to the symptoms of MS.

(b) Draw a diagram or provide a table showing the physiological differences (resting membrane potential value, ability to produce action potentials (AP), AP threshold, AP propagation, AP peak and AP duration) between MS patients and typical individuals.

(c) How does temperature alter action potential generation? Investigate the effect of temperature in alleviating the symptoms of MS in MS patients.

(d) How does temperature affect Na+ voltage-gated ion channels?

Answer 1

Multiple sclerosis is a disease of CNS in which due to destruction of protective sheet on neuron (mylein) it become weak and infirm. As a result of nerve injury, in this immune disorder the connection between brain and spinal cord is lost and hence, coordination of muscles is also lost.

Answer a. Axonal damage account for most of the neurodegenerative disorder. From the very early stage axonal damage cause the impaired proteins and organelles along the neuronal axon. This damage can be detected by the presence of APP (Amyloid Precursor protein), which keep flowing in normal conditions but get accumulated during the axonal loss. Another marker can be Neurofilament Heavy Chain (NFH) which is phosphorylated in healthy neurons but non-phosphorylated in diseased form.

The axonal loss by demyelination can be result of Wallerian degeneration (injury of nerve fibre) and axons injured degenerates. Due to demyelination, sodium channels get disperesed along the length of neuron inorder to fulfill increased energy demands for restoring nerve conduction. This increase in sodium channel requires large amount of sodium ions to be transported back by Na+/K+-ATPase pump into the extracellular space. Limited ATP concentration cause improper transport of sodium, resulting in its accumulation in axoplasm, ultimately causing impairment of Na+/K+-ATPase pumps in neuron. Since Na+ can be transported by Na+/Ca2+ exchanger, it allows entry of Ca2+ into neuron. This disturbed levels of Ca2+ in neuron cause death of spinal and cerebral neurons, activating proteases, impaired mitochondrial functioning, microtubules depolymerization and compromise axonal transport, ultimately resulting in multiple sclerosis.

Answer b.

As physiology shown in the image, due to myelin degeneracy the the pumps are lost affecting action potential a lot. The action potential of MS individual is low, AP threshold is very high, AP progression is lost, AP peak is comparatively high, AP duration is very low as compared to normal individuals.

Answer c. Temprature effect the Action Potential by creating electropositive and electronegative environment across the membrane. The change in temprature affects the amplitude of action potential affecting threshold, peak, duration of its progression. As temprature increase, ampliture of AP is decreased and duration is decreased.

In MS patients, even a small change in temprature effects the physiology to greater extent. AP conduction is low, sometimes at high temprature neurons get completely blocked.

Answer d. Increase in temprature increase the Na+ channel inactivation therefore increasing the demand of energy. This blockage cause inhibition of Na+ and K+ transport and Hence, action potential amplitude and duration is reduced.