Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1

Volatile anesthetics have been shown to activate various two-pore (2P) domain ... (...) channels such as TASK-1 and TREK-1 (TWIK-related acid-sensitive ... channel), and mice deficient in these channels are resistant to halothane-induced anesthesia. Here, we investigated whether ... 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 ... current in rat ventricular myocytes (which strongly express TASK-1) and selected human ... channels expressed in Xenopus laevis oocytes. In myocytes, etomidate decreased both inward rectifier ... (...) current (...) and acid-sensitive outward ... 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 ... 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. (ProQuest: ... denotes formulae/symbols omitted.)