Inhibitory effects of volatile anesthetics on currents produced on heterologous expresssion of KvLQT1 and minK in Xenopus oocytes

The slowly activating component of delayed rectifier K+ current (I-Ks) in the heart modulates the repolarization of cardiac action potential. We investigated the effects of the volatile anesthetics isoflurane and sevoflurane on cloned I-Ks coexpressed by KvLQTI and minK. Currents were induced following injection into oocytes of KvLQTI mRNA (10 ng) with or without minK mRNA (I ng), which were transcribed in vitro from cDNAs of normal rats hearts. A two-electrode voltage-clamp recording technique was used to investigate the effects of isoflurane (0-1.5 minimum alveolar concentration, MAC) and sevoflurane (0-1.5 MAC) on I-Ks (KvLQTI with minK) and KvLQTI alone currents. Currents were activated by step depolarizations to a series of potentials from a holding potential of -80 mV and measured as the deactivating tail current on repolarization to -60 mV. Following a 2-s depolarization to 40 mV, isoflurane and sevoflurane caused potency-dependent reductions in I-Ks and KvLQTI currents. Both of the volatile anesthetics tested accelerated the deactivation of I-Ks and KvLQTI currents. We conclude that the significant inhibitory effect of volatile anesthetics on the cloned I-Ks may partly contribute to the clinical observations of the prolongation of the ventricular repolarization (Q-T interval) by the anesthetics. (C) 2002 Elsevier Science Inc. All rights reserved.