Vesicular demyelination induced by raised intracellular calcium.

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Myelin vesiculation, a form of demyelination, has been observed with high concentrations of the divalent cation ionophore A23187.
• Previous studies indicated a link between ionophores and myelin damage, but the precise mechanisms and conditions were not fully elucidated.

Purpose of the Study:

• To investigate the effects of different concentrations of A23187 and ionomycin on myelin structure in isolated nerve segments.
• To determine the role of extracellular calcium (Ca2+) and other divalent cations in ionophore-induced demyelination.
• To assess the viability of Schwann cells during and after the demyelination process.

Main Methods:

• Incubation of rat ventral or dorsal root segments with varying concentrations of A23187 or ionomycin.
• Ultrastructural examination of myelin and Schwann cells.
• Assessment of Schwann cell viability using nigrosin exclusion.
• Modulation of extracellular Ca2+ concentrations and addition of other divalent cations or inhibitors.

Main Results:

• Low concentrations of A23187 induced delayed vesicular demyelination, while high concentrations caused rapid demyelination.
• Schwann cells remained viable initially, even with significant demyelination, but high ionophore concentrations led to eventual necrosis.
• Demyelination was strictly dependent on extracellular Ca2+ and could be prevented by specific inhibitors like Zn2+.
• Ionomycin also induced rapid, Ca2+-dependent myelin vesiculation.

Conclusions:

• Raised intracellular Ca2+ concentration can initiate vesicular demyelination in vital Schwann cells.
• This demyelination does not invariably result in Schwann cell death.
• The findings suggest a potential mechanism for vesicular demyelinating neuropathies.