Investigation of Mechanisms of Volatile Anesthetic Action by the Use of Gene Expression Techniques

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In the first year of this investigation, we investigated the effects of the volatile anesthetics isoflurane and sevoflurane on cloned I_<Ks> coexpressed by KvLQT1 and minK. Currents were induced following injection into oocytes of KvLQT1 mRNA with or without minK mRNA, 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 MAC) and sevoflurane (0-1.5 MAC) on I_<Ks> (KvLQT1 with mink) and KvLQT1 alone currents. Following a 2-s depolarization to +40 mV, isoflurane and sevoflurane caused potency-dependent reductions in I_<Ks> and KvLQT1 currents. Both of the volatile anesthetics tested accelerated the deactivation of I_<Ks> and KvLQT1 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. In the following year, we cloned another truncated splice variant of LCNQ1 from rat heart. Judging from the deleted sequence of the TCNQT1, the genomic structure of rat in this portion might be different from those of human and mouse. In the last year, we investigated the single-channel properties of the Ca^<2+> channels reconstituted with β_<2a> or β_<2c> subunit, and compared them with the properties of naive channel. In contrast to β_<2a> subunit, long-lasting closings were dominant in the Ca^<2+> channel with β^<2c> subunit and the native channel. The single-channel properties of Ca^<2+> channel with β_<2c> subunit were indistinguishable from those of native channel. Those findings suggest that β_<2c> subunit is one of the functional β subunits in the rat heart.