Knockout of the gene encoding the K(2P) channel KCNK7 does not alter volatile anesthetic sensitivity.
The molecular site of action for volatile anesthetics remains unknown despite many years of study. Members of the K(2P) potassium channel family, whose currents are potentiated by volatile anesthetics have emerged as possible anesthetic targets. In fact, a mouse model in which the gene for TREK-1 (KCNK2) has been inactivated shows resistance to volatile anesthetics. In this study we tested whether inactivation of another member of this ion channel family, KCNK7, in a knockout mouse displayed altered sensitivity to the anesthetizing effect of volatile anesthetics. KCNK7 knockout mice were produced by standard gene inactivation methods. Heterozygous breeding pairs produced animals that were homozygous, heterozygous or wild-type for the inactivated gene. Knockout animals were tested for movement in response to noxious stimulus (tail clamp) under varying concentrations of isoflurane, halothane, and desflurane to define the minimum alveolar concentration (MAC) preventing movement. Mice homozygous for inactivated KCNK7 were viable and indistinguishable in weight, general development and behavior from heterozygotes or wild-type littermates. Knockout mice (KCNK7-/-) displayed no difference in MAC for the three volatile anesthetics compared to heterozygous (+/-) or wild-type (+/+) littermates. Because inactivation of KCNK7 does not alter MAC, KCNK7 may play only a minor role in normal CNS function or may have had its function compensated for by other inhibitory mechanisms. Additional studies with transgenic animals will help define the overall role of the K(2P) channels in normal neurophysiology and in volatile anesthetic mechanisms.
Yost
C Spencer
CS
Department of Anesthesia and Perioperative Care, Medical Sciences Building, 513 Parnassus Avenue, University of California, San Francisco, CA 94143, USA. yosts@anesthesia.ucsf.edu
Oh
Irene
I
Eger
Edmond I
EI
Sonner
James M
JM
D000595:Amino Acid Sequence; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D051637:Shaker Superfamily of Potassium Channels / Q000235:genetics* / Q000502:physiology
D018685:Anesthetics, Inhalation; C513961:Kv1.7 potassium channel, mouse; D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D000077335:Desflurane; D007530:Isoflurane; D006221:Halothane