Effects of isoflurane and enflurane on intracellular Ca2+ mobilization in isolated cardiac myocytes.

Abstract

Enflurane and isoflurane may reduce cardiac contractility by altering mobilization and clearance of intracellular Ca2+ (Ca2+i). It was hypothesized that the negative inotropic actions of these agents involve limiting both membrane Ca2+ entry and altering intracellular Ca2+ release. The Ca2+i transients in rat ventricular myocytes loaded with fura-2 were recorded from a fluorescence microscope. Transients stimulated by membrane depolarization (suction electrode or elevated [K+]o) or 15 mM caffeine to release Ca2+ from the sarcoplasmic reticulum (SR) were analyzed for net amplitude, maximal rate of rise (VR), average rate of decline (VR) in [Ca2+]i, and duration. Enflurane and isoflurane reduced electrically stimulated Ca2+i transients in a dose-dependent manner. Enflurane depressed the Ca2+i transient amplitude more than isoflurane. Enflurane was more effective than isoflurane in reducing VR and VF in a concentration-dependent manner. At similar concentrations, both enflurane and isoflurane reduced the steady state elevation of [Ca2+]i by 50 mM K+o. Similarly, enflurane and isoflurane depressed caffeine-sensitive release of Ca2+ from the SR. The reduction in the Ca2+i transient because of SR Ca2+ release was greater in enflurane than in equal concentrations of isoflurane. Rates of elevation and decline in [Ca2+]i were also reduced in enflurane and isoflurane. The negative inotropic actions of enflurane and isoflurane involve a depression of Ca2+ influx during membrane excitation, as well as a reduction in SR Ca2+ release. Slowed rates of elevation in [Ca2+]i indicate that the latter mechanism may, in part, be caused by alterations in the kinetics of SR Ca2+ release.