ATP-sensitive potassium channel agonists do not alter MAC for isoflurane in rats.
The molecular mechanisms for general anesthesia are probably restricted to a sensitive set of target sites in the brain. Membrane hyperpolarization, brought about by increased potassium channel conductance, is coupled to opiate mu receptors, to alpha 2- adrenoceptors, and to muscarinic M2 receptors, all of which have anesthetic-sparing effects. One type of potassium channel, the ATP-sensitive potassium channel (IKATP) has well-known agonists: cromakalim and pinacidil. The effects on isoflurane minimum alveolar concentration (MAC) of intracerebroventricular injection of these IKATP agonists and of the alpha 2-adrenoceptor agonist clonidine were studied in rats. Baseline MAC was 1.60% (+/- 0.02 SEM) isoflurane in oxygen. 10 micrograms clonidine decreased MAC by 42% of baseline (P less than 0.05); 20 micrograms clonidine decreased MAC by 58% of baseline (P less than 0.01). Neither cromakalim (20 micrograms) nor pinacidil (20 micrograms) had any effect on MAC. The results imply that neither indiscriminate agonist action of volatile anesthetics at potassium channels nor indiscriminate inhibitory membrane hyperpolarization is likely to be a fundamental mechanism of anesthesia. Furthermore, potassium channels coupled to opiate mu receptors, to alpha 2 adrenoceptors, and to muscarinic M2 receptors are probably not the IKATP type.
Zucker
J R
JR
Department of Anesthesiology, University of Washington School of Medicine, Seattle.
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D019806:Cromakalim; D004347:Drug Interactions; D006146:Guanidines / Q000494:pharmacology; D007276:Injections, Intraventricular; D007530:Isoflurane / Q000378:metabolism*; D008297:Male; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D020110:Pinacidil; D007530:Isoflurane