REDUCED ANESTHETIC REQUIREMENTS, DIMINISHED BRAIN PLASMA-MEMBRANE CA2-ATPASE PUMPING, AND ENHANCED BRAIN SYNAPTIC PLASMA-MEMBRANE PHOSPHOLIPID METHYLATION IN DIABETIC RATS - EFFECTS OF INSULIN()

We have recently reported that streptozocin (STZ)-induced diabetes in rats was associated with i) reduced Ca2+ pumping by rat brain synaptic plasma membrane Ca2+-ATPase (PMCA) and ii) a substantial reduction in the partial pressures of halothane and xenon required to prevent move ment in response to stimulation (minimum effective dose or MED). MED f or both agents correlated well with the degree of hemoglobin glycation and with PMCA activity. We now report that MEDs for isoflurane, enflu rane, and desflurane were also substantially reduced in STZ-diabetic r ats, compared with placebo-injected controls. In addition, we examined the effect of insulin treatment, begun 2 weeks after induction of dia betes and continued for 3 more weeks, on isoflurane MED and on brain s ynaptic PMCA and phospholipid-N-methyltransferase I (PLMT I), another enzyme altered by inhalation anesthetics (1A). Partial treatment of di abetes, as indicated by decreased glycated hemoglobin (GHb) compared t o untreated diabetic rats, was associated with an isoflurane MED of 1. 05 vol%, intermediate between a control mean of 1.57 vol%, and an untr eated diabetic mean of 0.82 vol% (p<0.01), with a trend toward normali zation of both PMCA and PLMT I activity. We also examined isoflurane M ED and PMCA activity in the cerebrum and diencephalon-mesencephalon (D -M) of control and diabetic rats 2 and 12 weeks after induction of dia betes. Isoflurane MED was substantially reduced in diabetic rats from both treatment periods. Cerebral and D-M PMCA activities were each red uced to about 90% of control values 2 weeks after STZ induction. At 12 weeks, cerebral PMCA pumping in SPM from diabetic rats did not differ from control values, but PMCA pumping in SPM from the D-M was reduced to about 85% of control levels. Good correlation (r = 0.89, p < 0.01) was found between isoflurane MED and GHb, in all treatment groups. Th ese findings provide further evidence for an important role for PMCA i n IA action. They also suggest that anesthetic effects on the calcium pump, at specific anatomic sites may be of major importance in produci ng anesthesia.