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Volume 17, Number 16, Issue of August 15, 1997 pp. 6226-6235
Copyright ©1997 Society for Neuroscience

Differential Localization of Voltage-Dependent Calcium Channel alpha 1 Subunits at the Human and Rat Neuromuscular Junction

Received Dec. 9, 1996; revised May 5, 1997; accepted June 4, 1997.

Nicola C. Day1, Sarah J. Wood2, Paul G. Ince1, Stephen G. Volsen4, William Smith4, Clarke R. Slater2, and Pamela J. Shaw3

1 MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, United Kingdom, 2 Department of Neurobiology, School of Neurosciences, and 3 Division of Clinical Neurosciences, The Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, United Kingdom, and 4 Lilly Research Centre, Windlesham, Surrey GU20 6PH, United Kingdom

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 alpha 1 and regulatory beta  subunits. In this report, using fluorescence immunocytochemistry, we provide evidence that immunoreactivity to alpha 1A, alpha 1B, and alpha 1E 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, alpha 1A, is localized presynaptically in discrete puncta that may represent motor nerve terminals. We also demonstrate for the first time that alpha 1A and alpha 1B (which corresponds to N-type channels) may be localized in axon-associated Schwann cells and, further, that the alpha 1B subunit may be present in perisynaptic Schwann cells. In addition, the alpha 1E 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.

Key words: calcium channels; neuromuscular junction; motor neuron; Schwann cells; skeletal muscle; amyotrophic lateral sclerosis; rat; human




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