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-mu-g clonidine decreased MAC by 42% of baseline (P < 0.05); 20-mu-g clonidine decreased MAC by 58% of baseline (P < 0.01). Neither cromakalim (20-mu-g) nor pinacidil (20-mu-g) 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.