Knockout of the gene encoding the K2P channel KCNK7 does not alter volatile anesthetic sensitivity
| Autor: | Irene Oh, C. Spencer Yost, Edmond I. Eger, James M. Sonner |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Minimum alveolar concentration Potassium Channels Genotype Transgene Molecular Sequence Data Pharmacology Polymerase Chain Reaction Article Sevoflurane Mice Behavioral Neuroscience medicine Animals Amino Acid Sequence Mice Knockout Dose-Response Relationship Drug Isoflurane Sequence Homology Amino Acid Chemistry Anatomy Potassium channel Mice Inbred C57BL Pulmonary Alveoli Anesthetics Inhalation Knockout mouse Anesthetic Shaker Superfamily of Potassium Channels Female Halothane Desflurane medicine.drug |
| Zdroj: | Behavioural Brain Research. 193:192-196 |
| ISSN: | 0166-4328 |
| Popis: | The molecular site of action for volatile anesthetics remains unknown despite many years of study. Members of the K2P 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 wildtype for the inactivated gene. Knockout animals were tested for movement in response to noxious stimulus (tail clamp) under varying concentrations of isoflurane, sevoflurane 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 wildtype littermates. Knockout mice (KCNK7 −/−) displayed no difference in MAC for the three volatile anesthetics compared to heterozygous (+/−) or wildtype (+/+) 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 K2P channels in normal neurophysiology and in volatile anesthetic mechanisms. |
| Databáze: | OpenAIRE |
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