The long-term goal of the proposed research is three-fold, namely to understand: (i) the biophysical basis of conduction in normal mammalian nerve fibers; (ii) how it is disturbed in pathophysiological conditions; and (iii) finally, how such disturbance might be ameliorated. The rationale underlying the experiments is that the broad neurochemical and biophysical relationships that apply to nerve fibers in general may be obtained more conveniently from studies on non-myelinated (C) fibers, partly because their much larger axonal area per unit weight (due to their small diameter) makes metabolically-related factors much more prominent than in myelinated fibers, and partly because C fibers do not exhibit the non-uniform distribution of Na and K channels found in mammalian myelinated fibers where, for example, there is a high density of Na channels in the nodal axolemma with a much lower density in the internode. The main thrust of the present phase of the proposed research is to examine the nature of axon/Schwann cell interaction in the PNS - in particular to determine whether the satellite cells play a role (other than myelination) in directly supporting axonal conduction. Central to this approach is the determination of the function of the recently observed satellite-cell Na channels. One speculation is that the Schwann cells act as local sources of Na channels, which they synthesize for later transfer to the axolemma. The various facets of the proposed research address three issues: first, whether satellite cell Na channels do exist in both myelinated and non-myelinated nerve in vivo, a proposition that has recently been questioned; secondly, given that they exist, whether experimental evidence consistent with the transfer hypothesis can be gathered; and, finally, whether the degree of their expression can be modified experimentally, or can occur in pathophysiological conditions. Any knowledge on the factors that influence the basic mechanism of nerve conduction, and its description in pathophysiological conditions, must have relevance for demyelinating and other neurological diseases in general. However, there is a specific relevance of the present proposed research. For example, periods of remission, that may last for months or years, have long been known to be characteristic in Ms. Yet their basis remains largely unexplained. One possibility is that an increase in satellite-cell expression of Na channels increases the supply to the axolemma. The safety factor for transmission would increase, previously non-conducting axons would now function, and a period of remission would ensue.
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