Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1 |
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Authors: | Putzke C Hanley P J Schlichthörl G Preisig-Müller R Rinné S Anetseder M Eckenhoff R Berkowitz C Vassiliou T Wulf H Eberhart L |
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Affiliation: | Department of Anesthesiology and Critical Care Medicine, Philipps-University Marburg, Baldingerstrasse 1, 35043, Marburg, Germany. carolineputzke@gmx.de |
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Abstract: | Volatile anesthetics have been shown to activate various two-pore (2P) domain K+ (K2P) channels such as TASK-1 and TREK-1 (TWIK-related acid-sensitive K+ channel), and mice deficient in these channels are resistant to halothane-induced anesthesia. Here, we investigated whether K2P channels were also potentially important targets of intravenous anesthetics. Whole cell patch-clamp techniques were used to determine the effects of the commonly used intravenous anesthetics etomidate and propofol on the acid-sensitive K+ current in rat ventricular myocytes (which strongly express TASK-1) and selected human K2P channels expressed in Xenopus laevis oocytes. In myocytes, etomidate decreased both inward rectifier K+ (Kir) current (IK1) and acid-sensitive outward K+ current at positive potentials, suggesting that this drug may inhibit TASK channels. Indeed, in addition to inhibiting guinea pig Kir2.1 expressed in oocytes, etomidate inhibited human TASK-1 (and TASK-3) in a concentration-dependent fashion. Propofol had no effect on human TASK-1 (or TASK-3) expressed in oocytes. Moreover, we showed that, similar to the known effect of halothane, sevoflurane and the purified R-(–)- and S-(+)-enantiomers of isoflurane, without stereoselectivity, activated human TASK-1. We conclude that intravenous and volatile anesthetics have dissimilar effects on K2P channels. Human TASK-1 (and TASK-3) are insensitive to propofol but are inhibited by supraclinical concentrations of etomidate. In contrast, stimulatory effects of sevoflurane and enantiomeric isoflurane on human TASK-1 can be observed at clinically relevant concentrations. volatile anesthetics; etomidate; propofol; ion channels |
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