title: Ketamine, at clinical concentrations, does not alter the function of cardiac sarcoplasmic reticulum calcium release channels.
abstract: In the absence of sympathetically mediated stimulation, ketamine depresses myocardial contractility. This results from a decrease in the availability of intracellular Ca2+ for excitation-contraction coupling. Although sites of action other than the Ca2+ release channel of sarcoplasmic reticulum have been implicated, ketamine-induced alterations in Ca2+ efflux from the sarcoplasmic reticulum remain contentious. The purpose of the present study was to identify interactions of ketamine with the calcium release channel using sarcoplasmic reticulum enriched vesicles from porcine left ventricle. Ketamine did not alter [3H]ryanodine binding at concentrations of 1 mM or less, while binding was almost completely inhibited at 10 mM. Gating and conductance of SR Ca2+ channels studied in planar bilayers was not altered by clinical concentrations of ketamine over the range of physiologic cytoplasmic free Ca2+ concentrations. Channel inactivation was observed at 10 mM ketamine, well in excess of clinical concentrations. These findings indicate that clinical concentrations of ketamine do not alter the function of the Ca2+ release channel. Alterations in intracellular Ca2+ homeostasis that result in depression of myocardial contractility must therefore result from effects at other sites along the excitation-contraction coupling pathway.
authors.affiliation: Department of Anesthesiology, University of Wisconsin-Madison, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Connelly
authors.forename: C
authors.initials: C
authors.lastname: Ahern
authors.forename: R
authors.initials: R
authors.lastname: Coronado
mesh_terms: D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D012433:Ryanodine / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
chemical_list: D000778:Anesthetics, Dissociative; D015220:Calcium Channels; D012433:Ryanodine; D007649:Ketamine; D002118:Calcium