Reduced anesthetic requirements in aged rats: association with altered brain synaptic plasma membrane Ca(2+)-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 increased methyltransferase I (PLMTI) activity. In this study we evaluated concurrently anesthetic requirements and brain plasma membrane Ca(2+)-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 Fisher-344 rats. Halothane MED was also measured in 2 and 30 month old F344/BNF1 rats, a strain that undergoes aging with less debilitation. PMCA pumping and PLMTI activities were measured in synaptic plasma membranes (SPM) prepared from the cortex and diencephalon-mesencephalon (DM). For aged Fisher-344 rats, MEDs for halothane, desflurane, isoflurane and xenon were reduced to 81%, 82%, 67% and 86%, respectively, of young 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 SPM and 72% DM SPM, and PLMTI activity was increased to 133% in cortical SPM and 112% in DM SPM. The strong association between age and reduced anesthetic requirements for inhalational agents on the one hand and altered PMCA and PLMTI activity on the other lends support to the underlying hypothesis that PMCA and PLMTI may be involved in the production of the anesthetic state.
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
J L
JL
Horn
P K
PK
Janicki
G
G
Singh
A W
AW
Wamil
J J
JJ
Franks
D000375:Aging / Q000378:metabolism*; D000777:Anesthetics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D050941:Phosphatidyl-N-Methylethanolamine N-Methyltransferase; D050918:Phosphatidylethanolamine N-Methyltransferase; D051381:Rats; D011916:Rats, Inbred F344
D000777:Anesthetics; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D050941:Phosphatidyl-N-Methylethanolamine N-Methyltransferase; D000252:Calcium-Transporting ATPases; D002118:Calcium