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The stimulation of nicotinic acetylcholine receptor due to parasympathetic nerve activity causes an increase in intracellular Ca<jats:sup>2+<\/jats:sup>concentration and eventually downregulates melatonin production. Our previous report shows that rat pinealocytes have spontaneous and nicotine-induced Ca<jats:sup>2+<\/jats:sup>oscillations that are evoked by membrane depolarization followed by Ca<jats:sup>2+<\/jats:sup>influx through voltage-dependent Ca<jats:sup>2+<\/jats:sup>channels (VDCCs). These Ca<jats:sup>2+<\/jats:sup>oscillations are supposed to contribute to the inhibitory mechanism of melatonin secretion. Here we examined the involvement of large-conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>(BK<jats:sub>Ca<\/jats:sub>) channel conductance on the regulation of Ca<jats:sup>2+<\/jats:sup>oscillation and melatonin production in rat pinealocytes. Spontaneous Ca<jats:sup>2+<\/jats:sup>oscillations were markedly enhanced by BK<jats:sub>Ca<\/jats:sub>channel blockers (1 \u03bcM paxilline or 100 nM iberiotoxin). Nicotine (100 \u03bcM)-induced Ca<jats:sup>2+<\/jats:sup>oscillations were also augmented by paxilline. In contrast, spontaneous Ca<jats:sup>2+<\/jats:sup>oscillations were abolished by BK<jats:sub>Ca<\/jats:sub>channel opener [3 \u03bcM 12,14-dichlorodehydroabietic acid (diCl-DHAA)]. Under whole cell voltage-clamp configurations, depolarization-elicited outward currents were significantly activated by diCl-DHAA and blocked by paxilline. Expression analyses revealed that the \u03b1 and \u03b23 subunits of BK<jats:sub>Ca<\/jats:sub>channel were highly expressed in rat pinealocytes. Importantly, the activity of BK<jats:sub>Ca<\/jats:sub>channels modulated melatonin secretion from whole pineal gland of the rat. Taken together, BK<jats:sub>Ca<\/jats:sub>channel activation attenuates these Ca<jats:sup>2+<\/jats:sup>oscillations due to depolarization-synchronized Ca<jats:sup>2+<\/jats:sup>influx through VDCCs and results in a recovery of reduced melatonin secretion during parasympathetic nerve activity. BK<jats:sub>Ca<\/jats:sub>channels may play a physiological role for melatonin production via a negative-feedback mechanism.<\/jats:p>","DOI":"10.1152\/ajpcell.00342.2015","type":"journal-article","created":{"date-parts":[[2016,1,21]],"date-time":"2016-01-21T04:48:03Z","timestamp":1453351683000},"page":"C740-C747","source":"Crossref","is-referenced-by-count":13,"title":["Modulation of Ca<sup>2+<\/sup>oscillation and melatonin secretion by BK<sub>Ca<\/sub>channel activity in rat pinealocytes"],"prefix":"10.1152","volume":"310","author":[{"given":"Hiroya","family":"Mizutani","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 467-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisao","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya 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