REDUCED ANESTHETIC REQUIREMENTS IN AGED RATS - ASSOCIATION WITH ALTERED BRAIN SYNAPTIC PLASMA-MEMBRANE CA2-ATPASE PUMP AND PHOSPHOLIPID-METHYLTRANSFERASE-I ACTIVITIES()

Aging is associated with a decrease in anesthetic requirements. Animal models of aging manifest alteration of brain Ca2+ homeostasis and inc reased methyltransferase I (PLMTI) activity. In this study we evaluate d concurrently anesthetic requirements and brain plasma membrane Ca2+- ATPase (PMCA) and PLMTI activities in young and aged rats. Halothane, desflurane, isoflurane and xenon MEDs (lowest partial pressures that suppress a pain response) were measured in 2 and 25 month old, male Fi sher-344 rats. Halothane MED was also measured in 2 and 30 month old F 344/BNF1 rats, a strain that undergoes aging with less debilitation. P MCA pumping and PLMTI activities were measured in synaptic plasma memb ranes (SPM) prepared from the cortex and diencephalon-mesencephalon (D M). For aged Fisher-344 rats, MEDs for halothane, desflurane, isoflura ne and xenon were reduced to 81%, 82%, 67% and 86%, respectively, of y oung controls; PMCA activity was diminished to 91% in cortical SPM and 82% in DM SPM; and cortical and DM PLMTI activities were increased to 131% and 114% of young control. For F344/BNF1 rats, MED for halothane was reduced to 87%, PMCA activity was diminished to 90% in cortical S PM and 72% DM SPM, and PLMTI activity was increased to 133% in cortica l SPM and 112% in DM SPM. The strong association between age and reduc ed anesthetic requirements for inhalational agents on the one hand and altered PMCA and PLMTI activity on the other lends support to the und erlying hypothesis that PMCA and PLMTI may be involved in the producti on of the anesthetic state.