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 ⁴⁵C⁺⁺ 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 μM 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.