Gibbons S J, Núñez-Hernández R, Mazé G, Harrison N L
Department of Anesthesia, University of Chicago, Illinois 60637, USA.
Anesth Analg. 1996 Jun;82(6):1242-6. doi: 10.1097/00000539-199606000-00024.
Whole cell voltage clamp recordings were used to study the effects of two barbiturates, methohexital and pentobarbital, on inwardly rectifying K+ currents in the plasma membrane of a rat basophilic granulocyte cell line (RBL-1). Inwardly rectifying K+ currents are responsible for maintaining the resting membrane potential in a variety of cell types including skeletal and cardiac muscle, neurons, glia, blood cells, and endothelial cells. RBL-1 cells are unusual because the inward rectifier is the only apparent voltage-dependent current in these cells. Steps to command potentials between + 80 and -120 mV evoked only this strongly rectifying, rapidly developing current at membrane potentials more hyperpolarized than the reversal potential for K' ions. Extracellular Cs+ (10 mM) and Ba2+ (100 microM and 1 mM) blocked this current in a reversible and voltage-dependent manner. The voltage threshold for activation of the inwardly rectifying K+ current is dependent on the extracellular K+ concentration as predicted by the Nernst equation. Methohexital and pentobarbital reversibly inhibited the current in a concentration-dependent fashion with 50% inhibitory concentration (IC50) values of 145 microM and 218 microM respectively. The Hill slopes for both of these effects were approximately 1. The inhibition was not voltage dependent. These results indicate that fast inwardly rectifying K+ channels are potential molecular targets for barbiturates and could explain some of the diverse clinical effects of these drugs.
采用全细胞膜片钳记录技术，研究了两种巴比妥类药物——美索比妥和戊巴比妥对大鼠嗜碱性粒细胞系（RBL - 1）质膜内向整流钾电流的影响。内向整流钾电流负责维持多种细胞类型（包括骨骼肌、心肌、神经元、神经胶质细胞、血细胞和内皮细胞）的静息膜电位。RBL - 1细胞较为特殊，因为内向整流器是这些细胞中唯一明显的电压依赖性电流。当指令电位在 + 80 mV和 - 120 mV之间变化时，仅在膜电位比钾离子反转电位更超极化时诱发这种强烈整流、快速发展的电流。细胞外的铯离子（10 mM）和钡离子（100 μM和1 mM）以可逆且电压依赖的方式阻断该电流。内向整流钾电流激活的电压阈值取决于细胞外钾离子浓度，这与能斯特方程的预测一致。美索比妥和戊巴比妥以浓度依赖的方式可逆性抑制该电流，其50%抑制浓度（IC50）值分别为145 μM和218 μM。这两种效应的希尔系数均约为1。抑制作用不依赖电压。这些结果表明，快速内向整流钾通道是巴比妥类药物潜在的分子靶点，这可以解释这些药物的一些不同临床效应。
