{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T20:08:35Z","timestamp":1768680515965,"version":"3.49.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1997,12,1]]},"abstract":"<jats:p>Spontaneous secretion of the neurotransmitter acetylcholine in mammalian neuromuscular synapsis depends on the Ca<jats:sup>2+<\/jats:sup>content of nerve terminals. The Ca<jats:sup>2+<\/jats:sup>electrochemical gradient favors the entry of this cation. We investigated the possible involvement of three voltage-dependent Ca<jats:sup>2+<\/jats:sup>channels (VDCC) (L-, N-, and P\/Q-types) on spontaneous transmitter release at the rat neuromuscular junction. Miniature end-plate potential (MEPP) frequency was clearly reduced by 5 \u03bcM nifedipine, a blocker of the L-type VDCC, and to a lesser extent by the N-type VDCC blocker, \u03c9-conotoxin GVIA (\u03c9-CgTx, 5 \u03bcM). On the other hand, nifedipine and \u03c9-CgTx had no effect on K<jats:sup>+<\/jats:sup>-induced transmitter secretion. \u03c9-Agatoxin IVA (100 nM), a P\/Q-type VDCC blocker, prevents acetylcholine release induced by K<jats:sup>+<\/jats:sup>depolarization but failed to affect MEPP frequency in basal conditions. These results suggest that in the mammalian neuromuscular junction Ca<jats:sup>2+<\/jats:sup>enters nerve terminals through at least three different channels, two of them (L- and N-types) mainly related to spontaneous acetylcholine release and the other (P\/Q-type) mostly involved in depolarization-induced neurotransmitter release. Ca<jats:sup>2+<\/jats:sup>-binding molecule-related spontaneous release apparently binds Ca<jats:sup>2+<\/jats:sup>very rapidly and would probably be located very close to Ca<jats:sup>2+<\/jats:sup>channels, since the fast Ca<jats:sup>2+<\/jats:sup>chelator (BAPTA-AM) significantly reduced MEPP frequency, whereas EGTA-AM, exhibiting slower kinetics, had a lower effect. The increase in MEPP frequency induced by exposing the preparation to hypertonic solutions was affected by neither external Ca<jats:sup>2+<\/jats:sup>concentration nor L-, N-, and P\/Q-type VDCC blockers, indicating that extracellular Ca<jats:sup>2+<\/jats:sup>is not necessary to produce hyperosmotic neurosecretion. On the other hand, MEPP frequency was diminished by BAPTA-AM and EGTA-AM to the same extent, supporting the view that hypertonic response is promoted by \u201cbulk\u201d intracellular Ca<jats:sup>2+<\/jats:sup>concentration increases.<\/jats:p>","DOI":"10.1152\/ajpcell.1997.273.6.c1835","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T17:00:16Z","timestamp":1514134816000},"page":"C1835-C1841","source":"Crossref","is-referenced-by-count":54,"title":["Spontaneous acetylcholine release in mammalian neuromuscular junctions"],"prefix":"10.1152","volume":"273","author":[{"given":"Adriana","family":"Losavio","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones M\u00e9dicas A. Lanari, Universidad de Buenos Aires, 1427 Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Muchnik","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones M\u00e9dicas A. 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