title: Negative control mechanism with features of adaptation controls Ca2+ release in cardiac myocytes.
abstract: The central paradox of cardiac excitation-contraction coupling is that Ca(2+)-induced Ca2+ release (CICR), an inherently self-regenerating process, is finely graded by surface membrane Ca2+ current (ICa). By using FPL64176, a novel Ca2+ channel agonist that reduces inactivation of ICa, a rapid negative control mechanism was unmasked at the Ca2+ release level in isolated rat ventricular myocytes. This mechanism terminates CICR independently of the duration of trigger ICa and before the sarcoplasmic reticulum becomes depleted of Ca2+. In its ability to be reactivated by incremental increases in trigger ICa, this mechanism differs from conventional inactivation/desensitization and is similar to the mechanism of increment detection or adaptation described for intracellular Ca2+ release channels. These results indicate that ryanodine receptor adaptation regulates Ca2+ release in cardiac muscle, accounting for or contributing to the graded nature of CICR and, additionally, permitting stores to reload at later times during Ca2+ entry.
authors.affiliation: University of Texas Medical Branch, Department of Physiology & Biophysics, Galveston 77555-0641.
authors.forename: K
authors.initials: K
authors.lastname: Yasui
authors.forename: P
authors.initials: P
authors.lastname: Palade
authors.forename: S
authors.initials: S
authors.lastname: Györke
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002120:Calcium Channel Agonists; D011758:Pyrroles; C071658:FPL 64176; D012433:Ryanodine; D002118:Calcium