Gray A T, Zhao B B, Kindler C H, Winegar B D, Mazurek M J, Xu J, Chavez R A, Forsayeth J R, Yost C S
Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
Anesthesiology. 2000 Jun;92(6):1722-30. doi: 10.1097/00000542-200006000-00032.
Previous studies have identified a volatile anesthetic-induced increase in baseline potassium permeability and concomitant neuronal inhibition. The emerging family of tandem pore domain potassium channels seems to function as baseline potassium channels in vivo. Therefore, we studied the effects of clinically used volatile anesthetics on a recently described member of this family.
A cDNA clone containing the coding sequence of KCNK5 was isolated from a human brain library. Expression of KCNK5 in the central nervous system was determined by Northern blot analysis and reverse-transcription polymerase chain reaction. Functional expression of the channel was achieved by injection of cRNA into Xenopus laevis oocytes.
Expression of KCNK5 was detected in cerebral cortex, medulla, and spinal cord. When heterologously expressed in Xenopus oocytes, KCNK5 currents exhibited delayed activation, outward rectification, proton sensitivity, and modulation by protein kinase C. Clinical concentrations of volatile general anesthetics potentiated KCNK5 currents by 8-30%.
Human KCNK5 is a tandem pore domain potassium channel exhibiting delayed activation and sensitivity to volatile anesthetics and may therefore have a role in suppressing cellular excitability during general anesthesia.
先前的研究已证实挥发性麻醉剂可使基线钾通透性增加并伴随神经元抑制。新出现的串联孔结构域钾通道家族似乎在体内充当基线钾通道。因此，我们研究了临床使用的挥发性麻醉剂对该家族最近描述的一个成员的影响。
从人脑文库中分离出包含KCNK5编码序列的cDNA克隆。通过Northern印迹分析和逆转录聚合酶链反应确定KCNK5在中枢神经系统中的表达。通过将cRNA注射到非洲爪蟾卵母细胞中来实现该通道的功能性表达。
在大脑皮层、延髓和脊髓中检测到KCNK5的表达。当在非洲爪蟾卵母细胞中异源表达时，KCNK5电流表现出延迟激活、外向整流、质子敏感性以及蛋白激酶C的调节作用。挥发性全身麻醉剂的临床浓度使KCNK5电流增强了8%至30%。
人KCNK5是一种串联孔结构域钾通道，表现出延迟激活和对挥发性麻醉剂的敏感性，因此可能在全身麻醉期间抑制细胞兴奋性中发挥作用。
