Depression of Calcium Dynamics in Cardiac Myocytes-a Common Mechanism of Halogenated Hydrocarbon Anesthetics and Solvents

Abstract

Individual halogenated hydrocarbons (HC) have recently been demonstrated to depress Ca 2+ dynamics in cardiomyocytes during excitation-contraction coupling. In the present study, eight widely used HC were systematically compared for their effects on Ca 2+ dynamics in neonatal rat cardiomyocytes by means spectrofluorometric analysis of fura-2-Ca 2+-binding. Cells were exposed to dichloromethane (DCM), dichloroethane (DCE). 1,1,2-trichloroethane (112-TCE), trichloroethylene (TRI), halothane (HAL). 1,1,1-trichloroethane (111-TCE), perchloroethylene (PER), or pentachloroethane (PCE) in an environmentally controlled chamber. All HC tested decreased the height of electrically induced cytosolic free Ca 2+ ([Ca 2+] i) transients in a concentration-dependent and reversible manner (IC 50 0.15-18.06 mM) without significant effects on diastolic [Ca 2+] i. The increase in [Ca 2+] i induced by depolarization with 90 mM KCl was inhibited to a lesser degree. Investigations with thapsigargin (100 nM) and ryanodine (1 μM)-inhibitors of Ca 2+ release from the sarcoplasmic reticulum-provided evidence that the tonic Ca 2+ response after KCl depolarization depends mainly on sarcolemmal Ca 2+ influx. The potency of the eight HC to inhibit Ca 2+ dynamics in cardiomyocytes correlated with their octanol/water partition coefficients. Results support the hypothesis that alteration of Ca 2+ dynamics in cardiomyocytes is a common mechanism of cardiotoxic HC actions.