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SMOCs, Ito, and a component of Iso were Ca2+ dependent. SMOCs were spike shaped, occurred randomly, and had decay times appreciably longer than the time to peak. In the presence of cadmium or cobalt, SMOCs with pharmacologic properties identical to those seen in normal Ringer's could be generated at voltages of \u221220 mV and above. Their mean amplitude was Nernstian with respect to [K+]ext and they were blocked by tetraethylammonium. SMOCs were inhibited by iberiotoxin, were insensitive to apamin, and eliminated by nominally Ca2+-free solutions, indicative of BK-type Ca2+-activated K+ currents. Dihydropyridine Ca2+ channel antagonists and agonists decreased and increased SMOC frequencies, respectively. Ca2+ permeation through the kainic acid receptor had no effect. Blockade of organelle Ca2+ channels by ryanodine, or intracellular Ca2+ store depletion with caffeine, eradicated SMOCs. Internal Ca2+ chelation with 10 mM BAPTA eliminated SMOCs, whereas 10 mM EGTA had no effect. These results suggest a mechanism whereby Ca2+ influx through L-type Ca2+ channels and its subsequent amplification by Ca2+-induced Ca2+ release via the ryanodine receptor leads to a localized elevation of internal Ca2+. This amplified Ca2+ signal in turn activates BK channels in a discontinuous fashion, resulting in randomly occurring SMOCs.<\/jats:p>","DOI":"10.1085\/jgp.20028478","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:50:20Z","timestamp":1027702220000},"page":"355-372","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Mechanism of Generation of Spontaneous Miniature Outward Currents (SMOCs) in Retinal Amacrine Cells"],"prefix":"10.1085","volume":"119","author":[{"given":"Pratip","family":"Mitra","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, School of Medicine, State University of New York at Buffalo, Buffalo, NY 14214"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm M.","family":"Slaughter","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, School of Medicine, State University of New York at Buffalo, Buffalo, NY 14214"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2002,4,2]]},"reference":[{"key":"2023072919433773400_BIB1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1469-7793.2001.00099.x","volume":"534","year":"2001","journal-title":"J. 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