| Research Abstract |
The ERG1,ELK1,and KCNQ2/3 voltage-gated potassium channels were resistant to 2 minimum alveolar concentrations(MAC) of all general anesthetics tested(halothane, isoflurane, enflurane, F3,F6,pentobarbital, propofol, etomidate, alphaxalone, ketamine, ethanol, and hexanol). On the other hand, among inwardly rectifying potassium channels, GIRK channels were inhibited by volatile anesthetics, but not by intravenous anesthetics. The neuronal-type GIRK1/2 channels were inhibited by 2 MAC of halothane, isoflurane, enflurane, and F3, whereas the cardiac-type GIRK1/4 channels were inhibited only by F3. Conversely, IRK1 and ROMK1 channels were completely resistant to all anesthetics tested. Current responses of GIRK2 channels activated by m-opioid receptors were also inhibited by halothane. Thus, among inwardly rectifying potassium channels, GIRK channels, especially those composed of the GIRK2 subunit(neuronal subunit), are suggested to be sensitive to volatile anesthetics. Nitrous oxide (〜0.6 atmosphere) slightly but selectively potentiated GIRK channels(GIRK1/2,GIRK1/4, GIRK2 channels) by 〜10%. GIRK2 channels activated by mu-opioid receptors were also potentiated by nitrous oxide. Results of chimeric and multiple amino acid mutations suggest that the region containing the trans membrane domains, but not the pore-forming domain, may be involved in determining differences in anesthetic sensitivity between GIRK and IRK channels. Although inhibition of GIRK channel function by anesthetics is unlikely to account for the anesthetic actions, it may contribute to some excitatory side effects.
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