Nav channel expression undergoes two types of changes in demyelinating diseases that impact the pathophysiological properties of axons. The first type of change is Nav channel desegregation, leading to a dilution of the locally intense Na influx normally needed for saltatory conduction. The molecular mechanisms for normal clustering of Nav channels and channel desegregation in demyelination are being clarified at a rapid pace, and readers should consult Chapters 3, 7, 8, and 19 for greater details. The second type of change in demyelination is alteration in Nav gene expression. Demyelinated axons can lose certain Nav isoforms or acquire new Nav isoforms, resulting in new excitability properties in pathological axons. A notable example is the downregu-lation of Nav1.6 and acquisition of Nav1.2 in dysmyeli-nated axons and the inappropriate acquisition of Nav1.8 channels in Purkinje cells in demyelinating disorders. Readers should consult Chapter 7. We now turn to the main focus of this chapter: K and Ca channels on normal and demyelinated axons.
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