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Am J Physiol Cell Physiol 280: C1130-C1139, 2001;
0363-6143/01 $5.00
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Vol. 280, Issue 5, C1130-C1139, May 2001

Single-channel basis for conductance increase induced by isoflurane in Shaker H4 IR K+ channels

Jichang Li and Ana M. Correa

Department of Anesthesiology, School of Medicine, University of California, Los Angeles, California 90095-7115

Volatile anesthetics modulate the function of various K+ channels. We previously reported that isoflurane induces an increase in macroscopic currents and a slowing down of current deactivation of Shaker H4 IR K+ channels. To understand the single-channel basis of these effects, we performed nonstationary noise analysis of macroscopic currents and analysis of single channels in patches from Xenopus oocytes expressing Shaker H4 IR. Isoflurane (1.2% and 2.5%) induced concentration-dependent, partially reversible increases in macroscopic currents and in the time course of tail currents. Noise analysis of currents (70 mV) revealed an increase in unitary current (~17%) and maximum open probability (~20%). Single-channel conductance was larger (~20%), and opening events were more stable, in isoflurane. Tail-current slow time constants increased by 41% and 136% in 1.2% and 2.5% isoflurane, respectively. Our results show that, in a manner consistent with stabilization of the open state, isoflurane increased the macroscopic conductance of Shaker H4 IR K+ channels by increasing the single-channel conductance and the open probability.

general anesthetics; volatile anesthetics; voltage-gated channels; mechanisms of action; single channels


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