title: Inhibitory effects of volatile anesthetics on currents produced on heterologous expression of KvLQT1 and minK in Xenopus oocytes.
abstract: The slowly activating component of delayed rectifier K+ current (IKs) in the heart modulates the repolarization of cardiac action potential. We investigated the effects of the volatile anesthetics isoflurane and sevoflurane on cloned IKs coexpressed by KvLQT1 and minK. Currents were induced following injection into oocytes of KvLQT1 mRNA (10 ng) with or without minK mRNA (1 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 IKs (KvLQT1 with minK) and KvLQT1 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 IKs and KvLQT1 currents. Both of the volatile anesthetics tested accelerated the deactivation of IKs and KvLQT1 currents. We conclude that the significant inhibitory effect of volatile anesthetics on the cloned IKs may partly contribute to the clinical observations of the prolongation of the ventricular repolarization (Q-T interval) by the anesthetics.
authors.affiliation: Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, 060-8543 Sapporo, Hokkaido, Japan.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Chen
authors.forename: Michiaki
authors.initials: M
authors.lastname: Yamakage
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Tohse
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Namiki
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008738:Methyl Ethers / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000096:biosynthesis*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D000077149:Sevoflurane; D014982:Xenopus laevis
chemical_list: D018685:Anesthetics, Inhalation; D051668:Delayed Rectifier Potassium Channels; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496911:Kcnq1 protein, rat; D008738:Methyl Ethers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); D000077149:Sevoflurane; D007530:Isoflurane