KETAMINE, AT CLINICAL CONCENTRATIONS, DOES NOT ALTER THE FUNCTION OF CARDIAC SARCOPLASMIC-RETICULUM CALCIUM-RELEASE CHANNELS

In the absence of sympathetically mediated stimulation, ketamine depre sses myocardial contractility. This results from a decrease in the ava ilability of intracellular Ca2+ for excitation-contraction coupling. A lthough sites of action other than the Ca2+ release channel of sarcopl asmic reticulum have been implicated, ketamine-induced alterations in Ca2+ efflux from the sarcoplasmic reticulum remain contentious. The pu rpose of the present study was to identify interactions of ketamine wi th the calcium release channel using sarcoplasmic reticulum enriched v esicles from porcine left ventricle. Ketamine did not alter [H-3]ryano dine binding at concentrations of 1 mM or less, while binding was almo st completely inhibited at 10 mM. Gating and conductance of SR Ca2+ ch annels studied in planar bilayers was not altered by clinical concentr ations 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 tha t clinical concentrations of ketamine do not alter the function of the Ca2+ release channel. Alterations in intracellular Ca2+ homeostasis t hat result in depression of myocardial contractility must therefore re sult from effects at other sites along the excitation-contraction coup ling pathway.