Lu Zhongju, Gao Junyuan, Zuckerman Joan, Mathias Richard T, Gaudette Glenn, Krukenkamp Irvin, Cohen Ira S
Department of Physiology and Biophysics, Institute for Molecular Cardiology, State University of New York at Stony Brook, NY 11794-8661, USA.
Biochem Biophys Res Commun. 2007 Nov 9;363(1):194-6. doi: 10.1016/j.bbrc.2007.08.131. Epub 2007 Aug 31.
Ischemic preconditioning is a potent endogenous mechanism protecting many organs from the devastating effects of prolonged ischemia. In the heart, NO is one mediator of this myoprotective response thought to involve activation of the K(ATP) channel. Ischemic preconditioning is known to be induced by metabolic inhibition using sodium cyanide (NaCN) in single cardiomyocytes. In the present study, we show for the first time that the end effector channel activated by NaCN has been incorrectly identified. The channel activated is not K(ATP) but instead belongs to the relatively new family of two-pore domain potassium channels (K2P). Further when activated by metabolic ischemia, the amplitude of K2P current is directly modulated by activators and inhibitors of the NO pathway.
缺血预处理是一种强大的内源性机制,可保护许多器官免受长时间缺血的破坏性影响。在心脏中,一氧化氮(NO)是这种心肌保护反应的一种介质,被认为涉及ATP敏感性钾通道(K(ATP)通道)的激活。已知在单个心肌细胞中,使用氰化钠(NaCN)进行代谢抑制可诱导缺血预处理。在本研究中,我们首次表明,由NaCN激活的终末效应通道被错误识别。被激活的通道不是K(ATP)通道,而是属于相对较新的双孔结构域钾通道(K2P)家族。此外,当由代谢性缺血激活时,K2P电流的幅度可被NO途径的激活剂和抑制剂直接调节。