title: Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell.
abstract: Microprocessor-controlled changes of [free Ca2+] at the outer surface of the sarcoplasmic reticulum (SR) wrapped around individual myofibrils of a skinned canine cardiac Purkinje cell and aequorin bioluminescence recording were used to study the mechanism of Ca2+-induced release of Ca2+ from the SR. This Ca2+ release is triggered by a rapid increase of [free Ca2+] at the outer surface of the SR of a previously quiescent skinned cell. Ca2+-induced release of Ca2+ occurred under conditions that prevented any synthesis of ATP from ADP, was affected differentially by interventions that depressed the SR Ca2+ pump about equally, and required ionic conditions incompatible with all known Ca2+-releasing, uncoupled, partial reactions of the Ca2+ pump. Increasing the [free Ca2+]trigger up to an optimum increased the amount of Ca2+ released. A supraoptimum increase of [free Ca2+] trigger inactivated Ca2+-induced release of Ca2+, but partial inactivation was also observed at [free Ca2+] below that necessary for its activation. The amplitude of the Ca2+ release induced by a given increase of [free Ca2+] decreased when the rate of this increase was diminished. These results suggest that Ca2+-induced release of Ca2+ is through a channel across the SR membrane with time- and Ca2+-dependent activation and inactivation. The inactivating binding site would have a higher affinity for Ca2+ but a lower rate constant than the activating site. Inactivation appeared to be a first-order kinetic reaction of Ca2+ binding to a single site at the outer face of the SR with a Q10 of 1.68. The removal of inactivation was the slowest step of the cycle, responsible for a highly temperature-dependent (Q10 approximately 4.00) refractory period.
authors.forename: A
authors.initials: A
authors.lastname: Fabiato
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D004533:Egtazic Acid / Q000494:pharmacology; D006329:Heart Conduction System / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D010827:Physiology / Q000295:instrumentation; D011690:Purkinje Fibers / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors
chemical_list: D002147:Calmodulin; D007473:Ion Channels; D004533:Egtazic Acid; D002118:Calcium