SODIUM-CHANNELS AGGREGATE AT FORMER SYNAPTIC SITES IN INNERVATED AND DENERVATED REGENERATING MUSCLES

The role of innervation in the establishment and regulation of the syn aptic density of voltage-activated Na channels (NaChs) was investigate d at regenerating neuromuscular junctions. Rat muscles were induced to degenerate after injection of the Australian tiger snake toxin, notex in. The loose-patch voltage clamp technique was used to measure the de nsity and distribution of NaChs on muscle fibers regenerating with or without innervation. In either case, new myofibers formed within the o riginal basal lamina sheaths, and, NaChs became concentrated at regene rating endplates nearly as soon as they formed. The subsequent increas e in synaptic NaCh density followed a time course similar to postnatal muscles. Neuromuscular endplates regenerating after denervation, with no nerve terminals present, had NaCh densities not significantly diff erent from endplates regenerating in the presence of nerve terminals. The results show that the nerve terminal is not required for the devel opment of an enriched NaCh density at regenerating neuromuscular synap ses and implicate Schwann cells or basal lamina as the origin of the s ignal for NaCh aggregation. In contrast, the change in expression from the immature to the mature form of the NaCh isoform that normally acc ompanies development occurred only partially on muscles regenerating i n the absence of innervation. This aspect of NaCh regulation is thus d ependent upon innervation.