Differential Localization of Voltage-Dependent Calcium Channel α1Subunits at the Human and Rat Neuromuscular Junction

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Abstract
Neurotransmitter release is regulated by voltage-dependent calcium channels (VDCCs) at synapses throughout the nervous system. At the neuromuscular junction (NMJ) electrophysiological and pharmacological studies have identified a major role for P- and/or Q-type VDCCs in controlling acetylcholine release from the nerve terminal. Additional studies have suggested that N-type channels may be involved in neuromuscular transmission. VDCCs consist of pore-forming α1 and regulatory β subunits. In this report, using fluorescence immunocytochemistry, we provide evidence that immunoreactivity to α1A, α1B, and α1E subunits is present at both rat and human adult NMJs. Using control and denervated rat preparations, we have been able to establish that the subunit thought to correspond to P/Q-type channels, α1A, is localized presynaptically in discrete puncta that may represent motor nerve terminals. We also demonstrate for the first time that α1A and α1B (which corresponds to N-type channels) may be localized in axon-associated Schwann cells and, further, that the α1B subunit may be present in perisynaptic Schwann cells. In addition, the α1E subunit (which may correspond to R/T-type channels) seems to be localized postsynaptically in the muscle fiber membrane and concentrated at the NMJ. The possibility that all three VDCCs at the NMJ are potential targets for circulating autoantibodies in amyotrophic lateral sclerosis is discussed.