Discrete change in volatile anesthetic sensitivity in mice with inactivated tandem pore potassium ion channel TRESK.
BACKGROUND
We investigated the role of tandem pore potassium ion channel (K2P) TRESK in neurobehavioral function and volatile anesthetic sensitivity in genetically modified mice.


METHODS
Exon III of the mouse TRESK gene locus was deleted by homologous recombination using a targeting vector. The genotype of bred mice (wild type, knockout, or heterozygote) was determined using polymerase chain reaction. Morphologic and behavioral evaluations of TRESK knockout mice were compared with wild-type littermates. Sensitivity of bred mice to isoflurane, halothane, sevoflurane, and desflurane were studied by determining the minimum alveolar concentration preventing movement to tail clamping in 50% of each genotype.


RESULTS
With the exception of decreased number of inactive periods and increased thermal pain sensitivity (20% decrease in latency with hot plate test), TRESK knockout mice had healthy development and behavior. TRESK knockout mice showed a statistically significant 8% increase in isoflurane minimum alveolar concentration compared with wild-type littermates. Sensitivity to other volatile anesthetics was not significantly different. Spontaneous mortality of TRESK knockout mice after initial anesthesia testing was nearly threefold higher than that of wild-type littermates.


CONCLUSIONS
TRESK alone is not critical for baseline central nervous system function but may contribute to the action of volatile anesthetics. The inhomogeneous change in anesthetic sensitivity corroborates findings in other K2P knockout mice and supports the theory that the mechanism of volatile anesthetic action involves multiple targets. Although it was not shown in this study, a compensatory effect by other K2P channels may also contribute to these observations.
Department of Anesthesia and Pain Medicine, Ajou University Medical Center, Suwon, Korea.
Yun Jeong
YJ
Chae
Jianan
J
Zhang
Paul
P
Au
Marta
M
Sabbadini
Guo-Xi
GX
Xie
C Spencer
CS
Yost
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005838:Genotype; D018737:Hand Strength; D019417:Hindlimb Suspension; D006358:Hot Temperature; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D018685:Anesthetics, Inhalation; D004247:DNA; D017931:DNA Primers; D015221:Potassium Channels; C486498:Kcnk18 protein, mouse