Premium
Ca 2+ ‐dependent inactivation of Ca 2+ ‐induced Ca 2+ release in bullfrog sympathetic neurons
Author(s) -
Akita Tenpei,
Kuba Kenji
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.153833
Subject(s) - bullfrog , ryanodine receptor , chemistry , bapta , biophysics , depolarization , calcium , egta , membrane potential , medicine , endocrinology , receptor , biochemistry , biology , organic chemistry
We studied inactivation of Ca 2+ ‐induced Ca 2+ release (CICR) via ryanodine receptors (RyRs) in bullfrog sympathetic neurons. The rate of rise in [Ca 2+ ] i due to CICR evoked by a depolarizing pulse decreased markedly within 10–20 ms to a much slower rate despite persistent Ca 2+ entry and little depletion of Ca 2+ stores. The Ca 2+ entry elicited by the subsequent pulse within 50 ms, during which the [Ca 2+ ] i level remained unchanged, did not generate a distinct [Ca 2+ ] i rise. This mode of [Ca 2+ ] i rise was unaffected by a mitochondrial uncoupler, carbonyl cyanide p ‐trifluromethoxy‐phenylhydrazone (FCCP, 1 μ m ). Paired pulses of varying interval and duration revealed that recovery from inactivation became distinct ≥ 50 ms after depolarization and depended on [Ca 2+ ] i . The inactivation was prevented by BAPTA (≥ 100 μ m ) but not by EGTA (≤ 10 m m ), whereas the activation was less affected by BAPTA. When CICR was partially activated, some of the non‐activated RyRs were also inactivated directly. Thus, the inactivation in these neurons is induced by Ca 2+ binding to the high‐affinity regulatory sites residing very close to Ca 2+ channels and/or RyRs, although the sites for activation are located much closer to those Ca 2+ sources. The rate of [Ca 2+ ] i decay after the pulse decreased with increasing pulse duration longer than 10 ms, and this was abolished by BAPTA. Thus, some mechanism counteracting Ca 2+ 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 2+ signalling were discussed.