Ion Channels and Neuronal Dysfunction in Multiple Sclerosis

Abstract

W hat causes the signs and symptoms of multiple sclerosis (MS)? It is almost axiomatic to regard MS as a demyelinating disorder in which axonal conduction block, caused by loss of myelin, produces clinical deficits. In addition, during the past few years, increased attention has focused on axonal degeneration in MS. The available evidence suggests that demyelination provides a structural correlate for relapsingremitting disease while axonal degeneration, which may be associated with atrophy of the brain and spinal cord, produces nonremitting deficits.

Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: a potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury

“…In agreement with these results, blockade of sodium channels and NCX prevents axonal deterioration in anoxia (50,51). Interestingly, similar mechanisms have recently been implicated in MS and EAE (52,53). In addition, recent studies have suggested that ryanodine receptor-mediated release of calcium from the endoplasmic reticulum causes abnormal elevations in calcium concentrations within the axoplasm promoting injury during spinal cord ischemia (54).…”

Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: a potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury

“…In agreement with these results, blockade of sodium channels and NCX prevents axonal deterioration in anoxia (50,51). Interestingly, similar mechanisms have recently been implicated in MS and EAE (52,53). In addition, recent studies have suggested that ryanodine receptor-mediated release of calcium from the endoplasmic reticulum causes abnormal elevations in calcium concentrations within the axoplasm promoting injury during spinal cord ischemia (54).…”

A Mathematical Study of Effects of Alzheimer’s Drug Donepezil Hydrochloride on Neuronal Viscoelasticity and Action Potentials

“…The case δ AD = 0.75 shows plateau (delayed) potentials followed by higher frequency of firing which correspond to hyperexcitability seen in earlier stages of AD. Similar patterns of action potentials were observed experimentally in transgenic Na v1.8-null knockout DRG neurons [92], abnormal Na v1.8 expression in some neurons that may be linked to multiple sclerosis [93], and mutations of some sodium channels that cause persistent sodium currents linked to epilepsy [94,95]. The case δ AD = 0.5 (and lower values of δ) shows an almost cessation of action potentials that may be associated with later stages of AD [17].…”

The Impact of Anomalous Diffusion on Action Potentials in Myelinated Neurons

“…The increasing delay in the action potentials at the node of Ranvier with decreasing β (Figure 10b) looks like the shapes of the membrane potentials observed experimentally in transgenic Na v 1.8-null knockout DRG neurons ( [21], Figures 8b and9c). Abnormal Na v 1.8 expression in some neurons may be linked to multiple sclerosis in humans [22]. Mutations of some sodium channels can cause persistent sodium currents that, combined with the blockade of potassium and calcium currents, lead to prolonged plateau potentials in the neurons of mice [25] (also [24], Figure 1B).…”

Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: a potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury

“…In agreement with these results, blockade of sodium channels and NCX prevents axonal deterioration in anoxia (50,51). Interestingly, similar mechanisms have recently been implicated in MS and EAE (52,53). In addition, recent studies have suggested that ryanodine receptor-mediated release of calcium from the endoplasmic reticulum causes abnormal elevations in calcium concentrations within the axoplasm promoting injury during spinal cord ischemia (54).…”

A Mathematical Study of Effects of Alzheimer’s Drug Donepezil Hydrochloride on Neuronal Viscoelasticity and Action Potentials

“…The case δ AD = 0.75 shows plateau (delayed) potentials followed by higher frequency of firing which correspond to hyperexcitability seen in earlier stages of AD. Similar patterns of action potentials were observed experimentally in transgenic Na v1.8-null knockout DRG neurons [92], abnormal Na v1.8 expression in some neurons that may be linked to multiple sclerosis [93], and mutations of some sodium channels that cause persistent sodium currents linked to epilepsy [94,95]. The case δ AD = 0.5 (and lower values of δ) shows an almost cessation of action potentials that may be associated with later stages of AD [17].…”

The Impact of Anomalous Diffusion on Action Potentials in Myelinated Neurons

“…The increasing delay in the action potentials at the node of Ranvier with decreasing β (Figure 10b) looks like the shapes of the membrane potentials observed experimentally in transgenic Na v 1.8-null knockout DRG neurons ( [21], Figures 8b and9c). Abnormal Na v 1.8 expression in some neurons may be linked to multiple sclerosis in humans [22]. Mutations of some sodium channels can cause persistent sodium currents that, combined with the blockade of potassium and calcium currents, lead to prolonged plateau potentials in the neurons of mice [25] (also [24], Figure 1B).…”

Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: a potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury

“…In agreement with these results, blockade of sodium channels and NCX prevents axonal deterioration in anoxia (50,51). Interestingly, similar mechanisms have recently been implicated in MS and EAE (52,53). In addition, recent studies have suggested that ryanodine receptor-mediated release of calcium from the endoplasmic reticulum causes abnormal elevations in calcium concentrations within the axoplasm promoting injury during spinal cord ischemia (54).…”

A Mathematical Study of Effects of Alzheimer’s Drug Donepezil Hydrochloride on Neuronal Viscoelasticity and Action Potentials

“…The case δ AD = 0.75 shows plateau (delayed) potentials followed by higher frequency of firing which correspond to hyperexcitability seen in earlier stages of AD. Similar patterns of action potentials were observed experimentally in transgenic Na v1.8-null knockout DRG neurons [92], abnormal Na v1.8 expression in some neurons that may be linked to multiple sclerosis [93], and mutations of some sodium channels that cause persistent sodium currents linked to epilepsy [94,95]. The case δ AD = 0.5 (and lower values of δ) shows an almost cessation of action potentials that may be associated with later stages of AD [17].…”

The Impact of Anomalous Diffusion on Action Potentials in Myelinated Neurons

“…The increasing delay in the action potentials at the node of Ranvier with decreasing β (Figure 10b) looks like the shapes of the membrane potentials observed experimentally in transgenic Na v 1.8-null knockout DRG neurons ( [21], Figures 8b and9c). Abnormal Na v 1.8 expression in some neurons may be linked to multiple sclerosis in humans [22]. Mutations of some sodium channels can cause persistent sodium currents that, combined with the blockade of potassium and calcium currents, lead to prolonged plateau potentials in the neurons of mice [25] (also [24], Figure 1B).…”