Correa A M
Department of Anesthesiology, School of Medicine, University of California, Los Angeles, California 90095-1778, USA.
Am J Physiol. 1998 Oct;275(4):C1009-21. doi: 10.1152/ajpcell.1998.275.4.C1009.
The ShakerB K+ channel was used as a model voltage-gated channel to probe the interaction of volatile general anesthetics with gating mechanisms. The effects of three anesthetics, chloroform (CHCl3), isoflurane, and halothane, were studied using recombinant native and mutant Shaker channels expressed in Xenopus oocytes. Gating currents and macroscopic ionic currents were recorded with the cut-open oocyte voltage-clamp technique. The effects of CHCl3 and isoflurane on gating kinetics of noninactivating mutants were opposite, whereas halothane had no effect. The effects on ionic currents were also agent dependent: CHCl3 and halothane produced a reduction of the macroscopic conductance, whereas isoflurane increased it. The results indicate that the gating machinery of the channel is mostly insensitive to the anesthetics during activation until near the open state. The effects on the conductance are mainly due to changes in the transitions in and out of the open state. The data give support to direct protein-anesthetic interactions. The magnitude and nature of the effects invite reconsideration of Shaker-like K+ channels as important sites of action of general anesthetics.
将ShakerB钾离子通道用作模型电压门控通道，以探究挥发性全身麻醉药与门控机制的相互作用。使用在非洲爪蟾卵母细胞中表达的重组天然和突变型Shaker通道，研究了三种麻醉药氯仿（CHCl3）、异氟烷和氟烷的作用。采用切开卵母细胞电压钳技术记录门控电流和宏观离子电流。CHCl3和异氟烷对非失活突变体门控动力学的影响相反，而氟烷则无影响。对离子电流的影响也因药物而异：CHCl3和氟烷使宏观电导率降低，而异氟烷则使其增加。结果表明，通道的门控机制在激活过程中直至接近开放状态时，对麻醉药大多不敏感。对电导率的影响主要归因于进出开放状态转换的变化。这些数据支持蛋白质与麻醉药的直接相互作用。这些作用的大小和性质促使人们重新考虑类似Shaker的钾离子通道作为全身麻醉药重要作用位点的观点。
