{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T22:25:25Z","timestamp":1758925525588},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,6,22]],"date-time":"2005-06-22T00:00:00Z","timestamp":1119398400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2005,6,15]]},"abstract":"<jats:p>\u03b1\u2010Latrotoxin (\u03b1\u2010LT), a potent excitatory neurotoxin, increases spontaneous, as well as action potential\u2010evoked, quantal release at nerve terminals and increases hormone release from excitable endocrine cells. We have investigated the effects of \u03b1\u2010LT on single human, mouse and canine \u03b2\u2010cells. In isolated and combined measurements, \u03b1\u2010LT, at nanomolar concentrations, induces: (i) rises in cytosolic Ca<jats:sup>2+<\/jats:sup>, into the micromolar range, that are dependent on extracellular Ca<jats:sup>2+<\/jats:sup>; (ii) large conductance non\u2010selective cation channels; and (iii) Ca<jats:sup>2+<\/jats:sup>\u2010dependent insulin granule exocytosis, measured as increases in membrane capacitance and quantal release of preloaded serotonin. Furthermore, at picomolar concentrations, \u03b1\u2010LT potentiates depolarization\u2010induced exocytosis often without evidence of inducing channel activity or increasing cytosolic Ca<jats:sup>2+<\/jats:sup>. These results strongly support the hypothesis that \u03b1\u2010LT, after binding to specific receptors, has at least two complementary modes of action on excitable cells. (i) \u03b1\u2010LT inserts into the plasma membrane to form Ca<jats:sup>2+<\/jats:sup> permeable channels and promote Ca<jats:sup>2+<\/jats:sup> entry thereby triggering Ca<jats:sup>2+<\/jats:sup>\u2010dependent exocytosis in unstimulated cells. (ii) At lower concentrations, where its channel forming activity is hardly evident, \u03b1\u2010LT augments depolarization\u2010evoked exocytosis probably by second messenger\u2010induced enhancement of the efficiency of the vesicle recruitment or vesicle fusion machinery. We suggest that both modes of action enhance exocytosis from a newly described highly Ca<jats:sup>2+<\/jats:sup>\u2010sensitive pool of insulin granules activated by global cytosolic Ca<jats:sup>2+<\/jats:sup> concentrations in the range of \u223c1 \u03bc<jats:sc>m<\/jats:sc>.<\/jats:p>","DOI":"10.1113\/jphysiol.2005.082586","type":"journal-article","created":{"date-parts":[[2005,3,11]],"date-time":"2005-03-11T02:45:03Z","timestamp":1110509103000},"page":"783-799","source":"Crossref","is-referenced-by-count":12,"title":["\u03b1\u2010Latrotoxin increases spontaneous and depolarization\u2010evoked exocytosis from pancreatic islet \u03b2\u2010cells"],"prefix":"10.1113","volume":"565","author":[{"given":"Amelia M.","family":"Silva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"June","family":"Liu\u2010Gentry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam 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