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

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          15 August 1997
          : 17
          : 16
          : 6226-6235
          Affiliations
          [ 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
          Article
          PMC6568369 PMC6568369 6568369
          10.1523/JNEUROSCI.17-16-06226.1997
          6568369
          9236233
          db68fc8e-7850-4dcd-bc45-0224c30352b3
          Copyright © 1997 Society for Neuroscience
          History
          : 9 December 1996
          : 5 May 1997
          : 4 June 1997
          Categories
          Articles

          neuromuscular junction,human,skeletal muscle,amyotrophic lateral sclerosis,rat,calcium channels,motor neuron,Schwann cells

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