Clements Richard T, Terentyev Dmitry, Sellke Frank W
Department of Surgery, Cardiovascular Research Center, Cardiovascular Institute, Rhode Island Hospital and Alpert Medical School of Brown University.
Circ J. 2015;79(3):455-62. doi: 10.1253/circj.CJ-15-0015. Epub 2015 Jan 30.
Small- and large-conductance Ca(2+)-activated K(+)channels (SKCa and BKCa, respectively) may be important targets for therapeutic interventions in a variety of cardiac conditions. In cardiomyocytes, BKCa channels are localized to mitochondria where they beneficially modulate reactive oxygen species, mitochondrial Ca(2+), and respiration. In vascular smooth muscle cells, BKCa channels regulate vascular tone and promote vasodilation. Activation of BKCa channels has demonstrated significant cardioprotection following ischemic injury, including improved function and reduced infarct size. SKCa channels are expressed in both the membrane and mitochondria of cardiomyocytes. Modulation of cardiomyocyte SKCa channels may be beneficial for arrhythmia, heart failure, and ischemia. Mitochondrial SKCa channels may provide similar benefit to BKCa channels. In addition, activation of SKCa channels on the endothelium promotes vasodilation. This mini-review focuses on the modulation of cardiomyocyte BKCa and SKCa channels for cardioprotection and briefly address associated potential therapeutic benefits in the coronary circulation.
小电导和大电导钙激活钾通道（分别为SKCa和BKCa）可能是多种心脏疾病治疗干预的重要靶点。在心肌细胞中，BKCa通道定位于线粒体，在那里它们有益地调节活性氧、线粒体钙和呼吸作用。在血管平滑肌细胞中，BKCa通道调节血管张力并促进血管舒张。BKCa通道的激活已证明在缺血性损伤后具有显著的心脏保护作用，包括改善功能和减小梗死面积。SKCa通道在心肌细胞的细胞膜和线粒体中均有表达。调节心肌细胞SKCa通道可能对心律失常、心力衰竭和缺血有益。线粒体SKCa通道可能与BKCa通道具有相似的益处。此外，内皮细胞上SKCa通道的激活促进血管舒张。本综述聚焦于调节心肌细胞BKCa和SKCa通道以实现心脏保护，并简要探讨在冠脉循环中相关的潜在治疗益处。
