Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 6, Pages 3491-3496Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0437991100
Keywords
neuromuscular junction; alpha 1(A) knockout; paired-pulse facilitation; SNX-482; Ca2+-activated potassium channel
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Funding
- NINDS NIH HHS [NS 24067, R01 NS024067] Funding Source: Medline
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Transmission at the mouse neuromuscular junction normally relies on P/Q-type channels, but became jointly dependent on both Nand R-type Ca2+ channels when the P/Q-type channel alpha(1A) subunit was deleted. R-type channels lay close to Ca2+ sensors for exocytosis and I-K(Ca) channel activation, like the P/Q-type channels they replaced. In contrast, N-type channels were less well localized, but abundant enough to influence secretion strongly, particularly when action potentials were prolonged. Our data suggested that active zone structures may select among multiple Ca2+ channels in the hierarchy P/Q>R>N. The alpha(1A)-/- neuromuscular junction displayed several other differences from wild-type: lowered quantal content but greater ability to withstand reductions in the Ca2+/Mg2+ ratio, and little or no paired-pulse facilitation, the latter findings possibly reflecting compensatory mechanisms at individual release sites. Changes in presynaptic function were also associated with a significant reduction in the size of postsynaptic acetylcholine receptor clusters..
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