DIFFERENTIAL LOCALIZATION OF VOLTAGE-DEPENDENT CALCIUM-CHANNEL ALPHA(1) SUBUNITS AT THE HUMAN AND RAT NEUROMUSCULAR-JUNCTION

Neurotransmitter release is regulated by voltage-dependent calcium cha nnels (VDCCs) at synapses throughout the nervous system. At the neurom uscular junction (NMJ) electrophysiological and pharmacological studie s have identified a major role for P- and/or Q-type VDCCs in controlli ng acetylcholine release from the nerve terminal. Additional studies h ave suggested that N-type channels may be involved in neuromuscular tr ansmission. VDCCs consist of pore-forming alpha(1) and regulatory beta subunits units. In this report, using fluorescence immunocytochemistr y we provide evidence that immunoreactivity to alpha(1A), alpha(1B), a nd alpha(1E), subunits is present at both rat and human adult NMJs. Us ing control and denervated rat preparations, we have been able to esta blish that the subunit thought to correspond to P/Q-type channels, alp ha(1A), is localized presynaptically in discrete puncta that may repre sent motor nerve terminals. We also demonstrate for the first time tha t alpha(1A) and alpha(1B) (which corresponds to N-type channels) may b e localized in axon-associated Schwann cells and, further, that the al pha(1B) subunit may be present in perisynaptic Schwann cells. In addit ion, the alpha(1E) subunit (which may correspond to R/T-type channels) seems to be localized postsynaptically in the muscle fiber membrane a nd concentrated at the NMJ. The possibility that all three VDCCs at th e NMJ are potential targets for circulating autoantibodies in amyotrop hic lateral sclerosis is discussed.