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