Neuronal intracellular calcium concentrations are altered by anesthetics: relationship to membrane fluidization

The effects of anesthetic agents selected from various chemical classes (halothane, diethylether, pentobarbital and n-alkanols) on intracellular ionized Ca concentrations (Cai) were examined in mouse whole brain synaptosomes. Cai were determined using fura-2, a fluorescent Ca indicator. Halothane (3-6 mM), diethylether (100 mM) and n-alkanols (ethanol, butanol, pentanol and hexanol) increased resting Cai by 20 to 70%. Pentobarbital did not alter resting Cai when examined over a wide range of concentrations (0.01-1 mM). The ability of the anesthetics to increase resting Cai was correlated with their membrane fluidizing actions. Depolarization of synaptosomes by the addition of 50 mM KCI increased Cai by about 25%. The values of Cai measured after depolarization were reduced by diethylether (10-50 mM) and pentobarbital (0.05-1 mm) but were increased or unaltered by halothane and n-alkanols, respectively. All anesthetic agents tested except halothane reduced the net depolarization-dependent increase in Cai. These results provide a mechanism for anesthetic-induced neuronal hyperpolarization and predict effects of these agents on neurotransmitter release.