Ca2+-dependent inactivation of Ca2+-induced Ca2+ release in bullfrog sympathetic neurons.
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 microm). Paired pulses of varying interval and duration revealed that recovery from inactivation became distinct >or= 50 ms after depolarization and depended on [Ca(2+)](i). The inactivation was prevented by BAPTA (>or= 100 microm) but not by EGTA (<or= 10 mM), 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.
Akita
Tenpei
T
Laboratory of Anatomy and Physiology, Nagoya University of Arts and Sciences, School of Nutritional Sciences, Nisshin, Aichi 470-0196, Japan.
Kuba
Kenji
K
D000200:Action Potentials; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002491:Central Nervous System Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011892:Rana catesbeiana / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
D002491:Central Nervous System Agents; D012433:Ryanodine; D002110:Caffeine; D004533:Egtazic Acid; D019284:Thapsigargin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium