Diminished brain synaptic plasma membrane Ca(2+)-ATPase activity in rats with streptozocin-induced diabetes: association with reduced anesthetic requirements.
Recent evidence suggests that chronic hyperglycemia may inhibit plasma membrane Ca(2+)-ATPase (PMCA) in cells from several tissues. Inhalational anesthetics (IA) can inhibit brain synaptic PMCA activity. We proposed that diabetic rats may manifest chronic inhibition of brain synaptic PMCA and thus provide a model for testing the hypothesis that synaptic PMCA plays a key role in IA pharmacodynamics. Ca2+ pumping activity of PMCA was measured in cerebral synaptic plasma membrane (SPM) vesicles prepared from rats with streptozocin (STZ)-induced diabetes and from control, normoglycemic rats. Dose requirements for halothane and xenon were estimated in treated and untreated rats. Brain PMCA activity in hyperglycemic rats was depressed by about 8.4%, compared to controls. In vitro glycation also caused a significant decrease in PMCA pumping activity. Halothane requirement for STZ-hyperglycemic rats was dramatically 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 protein glycation. These results indicate that inhibition of brain synaptic PMCA in chronically hyperglycemic rats is associated with a significant reduction in IA requirement.
Janicki
P K
PK
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232.
Horn
J L
JL
Singh
G
G
Franks
W T
WT
Franks
J J
JJ
D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D006221:Halothane / Q000008:administration & dosage; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013570:Synaptic Membranes / Q000201:enzymology*; D014978:Xenon / Q000008:administration & dosage
D018685:Anesthetics, Inhalation; D001786:Blood Glucose; D014978:Xenon; D000252:Calcium-Transporting ATPases; D006221:Halothane