DIMINISHED BRAIN SYNAPTIC PLASMA-MEMBRANE CA2-ATPASE ACTIVITY IN RATSWITH STREPTOZOCIN-INDUCED DIABETES - ASSOCIATION WITH REDUCED ANESTHETIC REQUIREMENTS()

Recent evidence suggests that chronic hyperglycemia may inhibit plasma membrane Ca2+-ATPase (PMCA) in cells from several tissues. Inhalation al anesthetics (IA) can inhibit brain synaptic PMCA activity. We propo sed that diabetic rats may manifest chronic inhibition of brain synapt ic PMCA and thus provide a model for testing the hypothesis that synap tic PMCA plays a key role in IA pharmacodynamics. Ca2+ pumping activit y of PMCA was measured in cerebral synaptic plasma membrane (SPM) vesi cles prepared from rats with streptozocin (STZ)-induced diabetes and f rom control, normoglycemic rats. Dose requirements for halothane and x enon were estimated in treated and untreated rats. Brain PMCA activity in hyperglycemic rats was depressed by about 8.4%, compared to contro ls. In vitro glycation also caused a significant decrease in PMCA pump ing activity. Halothane requirement for STZ-hyperglycemic rats was dra matically reduced to about 65% of control. Xenon requirement was also significantly reduced, to 88% of control. Correlation of IA dose with percent glycated hemoglobin for each rat revealed a strong association between reduced requirements for halothane or xenon and increased pro tein glycation. These results indicate that inhibition of brain synapt ic PMCA in chronically hyperglycemic rats is associated with a signifi cant reduction in IA requirement.