Mutation of KCNK5 or Kir3.2 potassium channels in mice does not change minimum alveolar anesthetic concentration.
Several reports suggest that clinically used concentrations of inhaled anesthetics can increase conductance through noninactivating potassium channels and that the resulting hyperpolarization might decrease excitability, thereby leading to the anesthetic state. We speculated that animals deficient in such potassium channels might be resistant to the effects of anesthetics. Thus, in the present study, we measured the minimum alveolar anesthetic concentration (MAC) needed to prevent movement in response to a noxious stimulus in 50% of adult mice lacking functional KCNK5 potassium channel subunits and compared these results with those for heterozygous and wild-type mice. We also measured MAC in weaver mice that had a mutation in the potassium channel Kir3.2 and compared the resulting values with those for wild-type mice. MAC values for desflurane, halothane, and isoflurane for KCNK5-deficient mice and isoflurane MAC values for weaver mice did not differ from MAC values found in control mice. Our results do not support the notion that these potassium channels mediate the capacity of inhaled anesthetics to produce immobility. In addition, we found that the weaver mice did not differ from control mice in their susceptibility to convulsions from the nonimmobilizers flurothyl [di-(2,2,2,-trifluoroethyl)ether] or 2N (1,2-dichlorohexafluorocyclobutane). IMPLICATIONS: Mice harboring mutations in either of two different potassium channels have minimum alveolar anesthetic concentration (MAC) values that do not differ from MAC values found in control mice. Such findings do not support the notion that these potassium channels mediate the capacity of inhaled anesthetics to produce immobility in the face of noxious stimulation.
Pubmed ID: 12707131 RIS Download
Anesthetics, Inhalation | Animals | Cells, Cultured | Convulsants | DNA | Electroporation | Flurothyl | Genetic Vectors | Halothane | Isoflurane | Mice | Mice, Neurologic Mutants | Mutation | Potassium Channels | Potassium Channels, Inwardly Rectifying | Potassium Channels, Tandem Pore Domain | Pulmonary Alveoli | Reverse Transcriptase Polymerase Chain Reaction