Journal of pharmacological sciences
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Comparative Study
Sevoflurane inhibition of the slowly activating delayed rectifier K+ current in guinea pig ventricular cells.
Single ventricular cells were enzymatically isolated from guinea pig hearts and the effects of sevoflurane on the delayed rectifier K(+) current were investigated by the patch clamp method. The rapidly (I(Kr)) and slowly activating delayed rectifier K(+) current (I(Ks)) were isolated using chromanol 293B, a selective blocker for I(Ks) or E4031 (N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl]methanesulfonamide dihydrochloride), a blocker for I(Kr). Sevoflurane and halothane decreased I(Ks) in a concentration-dependent manner with an IC(50) value of 0.38 mM for sevoflurane and 1.05 mM for halothane. ⋯ Under the current clamp, sevoflurane prolonged the action potential duration in a reversible manner and this effect was more marked when I(Kr) was inhibited by E4031. The results suggest that sevoflurane inhibits I(Ks), and not I(Kr), in a concentration-dependent manner at clinically relevant concentrations. The resulting prolongation of ventricular repolarization may partly account for the clinical observation of excessive QT prolongation by these anesthetics.