{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T16:50:36Z","timestamp":1698771036965},"reference-count":43,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2008,7,14]],"date-time":"2008-07-14T00:00:00Z","timestamp":1215993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2008,7,15]]},"abstract":"<jats:p>We studied inactivation of Ca<jats:sup>2+<\/jats:sup>\u2010induced Ca<jats:sup>2+<\/jats:sup> release (CICR) via ryanodine receptors (RyRs) in bullfrog sympathetic neurons. The rate of rise in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> due to CICR evoked by a depolarizing pulse decreased markedly within 10\u201320 ms to a much slower rate despite persistent Ca<jats:sup>2+<\/jats:sup> entry and little depletion of Ca<jats:sup>2+<\/jats:sup> stores. The Ca<jats:sup>2+<\/jats:sup> entry elicited by the subsequent pulse within 50 ms, during which the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> level remained unchanged, did not generate a distinct [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> rise. This mode of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> rise was unaffected by a mitochondrial uncoupler, carbonyl cyanide <jats:italic>p<\/jats:italic>\u2010trifluromethoxy\u2010phenylhydrazone (FCCP, 1 \u03bc<jats:sc>m<\/jats:sc>). Paired pulses of varying interval and duration revealed that recovery from inactivation became distinct \u2265 50 ms after depolarization and depended on [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. The inactivation was prevented by BAPTA (\u2265 100 \u03bc<jats:sc>m<\/jats:sc>) but not by EGTA (\u2264 10 m<jats:sc>m<\/jats:sc>), whereas the activation was less affected by BAPTA. When CICR was partially activated, some of the non\u2010activated RyRs were also inactivated directly. Thus, the inactivation in these neurons is induced by Ca<jats:sup>2+<\/jats:sup> binding to the high\u2010affinity regulatory sites residing very close to Ca<jats:sup>2+<\/jats:sup> channels and\/or RyRs, although the sites for activation are located much closer to those Ca<jats:sup>2+<\/jats:sup> sources. The rate of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> decay after the pulse decreased with increasing pulse duration longer than 10 ms, and this was abolished by BAPTA. Thus, some mechanism counteracting Ca<jats:sup>2+<\/jats:sup> clearance is induced after full inactivation and potentiated during the pulse. Possible models for RyR inactivation were proposed and the roles of inactivation in Ca<jats:sup>2+<\/jats:sup> signalling were discussed.<\/jats:p>","DOI":"10.1113\/jphysiol.2008.153833","type":"journal-article","created":{"date-parts":[[2008,5,16]],"date-time":"2008-05-16T00:34:34Z","timestamp":1210898074000},"page":"3365-3384","source":"Crossref","is-referenced-by-count":6,"title":["Ca<sup>2+<\/sup>\u2010dependent inactivation of Ca<sup>2+<\/sup>\u2010induced Ca<sup>2+<\/sup> release in bullfrog sympathetic neurons"],"prefix":"10.1113","volume":"586","author":[{"given":"Tenpei","family":"Akita","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Kuba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,7,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.116.5.697"},{"key":"e_1_2_6_3_1","first-page":"S139","volume":"52","author":"Akita T","year":"2002","journal-title":"Jpn J Physiol"},{"key":"e_1_2_6_4_1","volume":"366","author":"Akita T","year":"2003","journal-title":"Abstr Soc 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