Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States.
Semin Cell Dev Biol. 2011 Apr;22(2):166-70. doi: 10.1016/j.semcdb.2010.09.013. Epub 2010 Oct 8.
The coordinate activities of ion channels and transporters regulate myocyte membrane excitability and normal cardiac function. Dysfunction in cardiac ion channel and transporter function may result in cardiac arrhythmias and sudden cardiac death. While the past fifteen years have linked defects in ion channel biophysical properties with human disease, more recent findings illustrate that ion channel and transporter localization within cardiomyocytes is equally critical for normal membrane excitability and tissue function. Ankyrins are a family of multifunctional adapter proteins required for the expression, membrane localization, and regulation of select cardiac ion channels and transporters. Notably, loss of ankyrin expression in mice, and ankyrin loss-of-function in humans is now associated with defects in myocyte excitability and cardiac physiology. Here, we provide an overview of the roles of ankyrin polypeptides in cardiac physiology, as well as review other recently identified pathways required for the membrane expression and regulation of key cardiac ion channels and transporters.
离子通道和转运体的协调活动调节心肌细胞膜的兴奋性和正常心脏功能。心脏离子通道和转运体功能障碍可导致心律失常和心脏性猝死。尽管在过去的 15 年中，人们已经将离子通道的生物物理特性缺陷与人类疾病联系起来，但最近的发现表明，离子通道和转运体在心肌细胞内的定位对于正常的膜兴奋性和组织功能同样至关重要。锚蛋白是一类多功能衔接蛋白，对于某些心脏离子通道和转运体的表达、膜定位和调节是必需的。值得注意的是，在小鼠中缺失锚蛋白表达以及在人类中锚蛋白功能丧失，现在与心肌细胞兴奋性和心脏生理学缺陷相关。在这里，我们概述了锚蛋白多肤在心脏生理学中的作用，并回顾了其他最近确定的途径，这些途径对于关键心脏离子通道和转运体的膜表达和调节是必需的。
