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Penn Researchers Prove "Short-Cut" Function Of Myelin Sheath Channel: BetterUnderstanding Of Myelin Should Lead To Therapies For Neuropathies

h is a unique cellular adaptation found in most vertebrates. "It's very peculiar in that it's like a sleeping bag all rolled up around the axon, the nerve cell inside," remarks Scherer. The sheath allows for the fast conduction times seen in higher vertebrates. Because of its many layers, the sheath might limit diffusion of necessary substances to and from the cell. "But nature has circumvented that problem with gap junctions," he explains.

"These channels provide a radial path for ions and small molecules that we believe is a thousand times shorter and a million times faster than traveling the entire circumference of the sheath," says Balice-Gordon. "We used intracellular dye injections in cultures of myelinating cells and video microscopy to directly demonstrate that this short-cut exists."

In labs all over the world, about 160 mutations have been discovered for connexin32. One group of mutated proteins can still form functional gap junctions, but it remains to be seen how these result in inherited neuropathies. In general, though, as the myelinating cells break down due to these mutations, they impart pathological changes onto the axon. "The mechanism of that might be related to potassium ion movement through the gap junctions, but this is just a hypothesis right now," states Scherer.

"Certainly in the narrowest sense this research ought to lead to some treatments for CMTX," adds Scherer. "We ought to be able to someday design therapies based on our growing knowledge of how the mutations affect the sheath and the passage of ions through gap junctions." So far, the team has been able to express in transgenic mice both normal and mutant connexin32 genes in myelinating cells. This work indicates that these mutations have altered the function of the cells and could account for the demyelinating neuropathies seen in the transgenic mice.

This research was supported by grants from the National Institutes of Health and the Mus
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Contact: Karen Young Kreeger
kreeger@mail.med.upenn.edu
(215) 614-0290
University of Pennsylvania School of Medicine
24-Aug-1998


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