The ability of eight widely used halogenated hydrocarbons (HC) to depress calcium (Ca) ion dynamics in rat cardiomyocytes during excitation/contraction coupling was examined. Cardiac ventricular cells isolated from neonatal Sprague-Dawley-rats were exposed to dichloromethane (75092) (DCM), dichloroethane (1300216) (DCE), 1,1,2- trichloroethane (79005) (1,1,2-TCE), trichloroethylene (79016) (TRI), halothane (151677) (HAL), 1,1,1-trichloroethane (71556) (1,1,1-TCE), perchloroethylene (127184) (PER), or perchloroethane (67721) (PCE) in a suffusion chamber. Measurement of Ca2+ was performed by incubation of myocytes with fura-2 prior to HC exposure and analysis by phase contrast microscope and dual excitation spectrofluorometer. All HCs induced a reversible reduction of amplitude of electrically induced Ca+2 without significant effects on diastolic Ca+2. Overt damage to the ventricular myocytes was indicated by absence of fura-2 loss through leaky membranes. The accumulation of Ca+2 caused by depolarization with 90 nanomolar potassium-chloride (7447407) (KCl) was inhibited as well, but to a lesser degree. A moderate inhibition of electrically induced Ca+2 was observed in myocytes treated with inhibitors of Ca+2 release. Evidence that the tonic Ca+2 response after depolarization depended primarily on the sarcolemmal Ca+2 influx was observed. The HC appeared to affect the release and accumulation of Ca+2 by the sarcoplasmic reticulum. The authors conclude that changes of Ca+2 dynamics in cardiomyocytes may be a common mechanism of HC cardiotoxicity.
NIOSH-Author; Chlorinated-hydrocarbons; Cell-cultures; Cardiac-function; Toxic-effects; Fluorometry; Cell-biology; In-vitro-study; Anesthetics; Chlorinated-hydrocarbons; Ion-transport;
Author Keywords: Cardiomyocytes; Fura-2; Ca2+; transients; KCl depolarization; Halogenated hydrocarbons; sarcolemmal membrane; Sarcoplasmic reticulum