Stable inhibition of brain synaptic plasma membrane calcium ATPpase in rats anesthetized with halothane

Background: The authors recently showed that plasma membrane Ca²⁺- ATPase (PMCA) activity in cerebral synaptic plasma membrane (SPM) is diminished in a dose-related fashion during exposure in vitro to halothane, isoflurane, xenon, and nitrous oxide at clinically relevant partial pressures. They have now extended their work to in vivo studies, examining PMCA pumping in SPM obtained from control rats decapitated without anesthetic exposure, from rats decapitated during halothane anesthesia, and from rats decapitated after recovery from halothane anesthesia. Methods: Three treatment groups were studied: 1) C, control rats that were decapitated without anesthetic exposure, 2) A, anesthetized rats exposed to 1 minimum effective dose (MED) for 20 min and then decapitated, and 3) R, rats exposed to 1 MED for 20 min and then decapitated after recovery from anesthesia, defined as beginning to groom. Plasma membrane Ca²⁺-ATPase pumping and Ca²⁺-dependent ATPase hydrolytic activity, as well as sodium-calcium exchanger activity and Na⁺K⁺ -ATPase hydrolytic activity, were assessed in cerebral SPM. In addition, halothane effect on smooth endoplasmic reticulum Ca²⁺-ATPase (SERCA) was examined. Results: Plasma membrane Ca²⁺-ATPase transport of Ca²⁺ into SPM vesicles from anesthetized rats was reduced to 71% of control (P < 0.01) compared with 113% of control for the recovered group (NS). No depression by halothane of SERCA activity, sodium-calcium exchanger, or Na⁺ -K⁺-ATPase activity was noted among the CAR treatment groups. Conclusions: Plasma membrane Ca²⁺-ATPase is selectively and stably inhibited in cerebral SPM from rats killed while anesthetized with halothane, compared with rats killed without anesthesia or after recovery from anesthesia. The studies described in this report, in conjunction with previously re-ported inhibition of PMCA activity in vitro by a wide range of anesthetic agents, indicate a relationship between inhibition of PMCA and action of inhalational anesthetics.