The effects of volatile anesthetics on Ca++ mobilization in rat hepatocytes

This study provides direct evidence that in hepatocytes, intracellular Ca++ is released from internal stores by halothane, enflurane, and isoflurane. Hepatocytes isolated from rat livers were used fresh or treated with saponin and then incubated in 45Ca++ media. The uptake of 45Ca++ by hepatocytes was maximal following 13-16 min of incubation (untreated or saponin-treated) and the effects of various agents on the release of 45Ca++ was studied following maximal loading. The agents used included halothane, enflurane, isoflurane, and several putative intracellular second messengers. The anesthetics, to various degrees, all stimulated a significant release of 45Ca++ from internal stores at concentrations that were at or less than clinical concentrations. The release of intracellular 45Ca++ by each of the anesthetic agents was dose-dependent with halothane and enflurane being equally potent at concentrations equivalent to 1 MAC exposure. The halothane-induced release was only somewhat suppressed by preincubation in either 2 mM LaCL3 or 10 microM dantrolene, both suggested Ca++ channel blockers. Transient increases in intracellular Ca++ regulates a number of enzyme systems, including glycogenolysis, while prolonged elevation in Ca++ concentrations have been implicated in the mechanism of hepatotoxicity.