STABLE INHIBITION OF BRAIN SYNAPTIC PLASMA-MEMBRANE CALCIUM-ATPASE INRATS ANESTHETIZED WITH HALOTHANE

Background: The authors recently showed that plasma membrane Ca2+-ATPa se (PMCA) activity in cerebral synaptic plasma membrane (SPM) is dimin ished in a dose-related fashion during exposure in vitro to halothane, isoflurane, xenon, and nitrous oxide at clinically relevant partial p ressures. They have now extended their work to in vivo studies, examin ing PMCA pumping in SPM obtained from control rats decapitated without anesthetic exposure, from rats decapitated during halothane anesthesi a, 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 decapita ted, and 3) R, rats exposed to 1 MED for 20 min and then decapitated a fter recovery from anesthesia, defined as beginning to groom. Plasma m embrane Ca2+-ATPase pumping and Ca2+-dependent ATPase hydrolytic activ ity, as well. as sodium-calcium exchanger activity and Na+-K+-ATPase h ydrolytic activity, were assessed in cerebral SPM. In addition, haloth ane effect on smooth endoplasmic reticulum Ca2+-ATPase (SERCA) was exa mined. 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 dep ression by halothane of SERCA activity, sodium-calcium exchanger, or N a+-K+-ATPase activity was noted among the CAR treatment groups. Conclu sions: Plasma membrane Ca2+-ATPase is selectively and stably inhibited in cerebral SPM from rats killed while anesthetized with halothane, c ompared with rats killed without anesthesia or after recovery from ane sthesia. The studies described in this report, in conjunction with pre viously reported inhibition of PMCA activity in via vitro by a wide ra nge of anesthetic agents, indicate a relationship between inhibition o f PMCA and action of inhalational anesthetics.