Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany; HCR, Heidelberg Center for Heart Rhythm Disorders, University Hospital Heidelberg, Heidelberg, Germany.
Institute for Physiology and Pathophysiology, Vegetative Physiology and Marburg Center for Mind, Brain and Behavior - Philipps-University Marburg, Marburg, Germany.
Prog Biophys Mol Biol. 2021 Jan;159:126-135. doi: 10.1016/j.pbiomolbio.2020.05.007. Epub 2020 Jun 15.
TWIK-related K channel (TREK-1) two-pore-domain potassium (K) channels mediate background potassium currents and regulate cellular excitability in many different types of cells. Their functional activity is controlled by a broad variety of different physiological stimuli, such as temperature, extracellular or intracellular pH, lipids and mechanical stress. By linking cellular excitability to mechanical stress, TREK-1 currents might be important to mediate parts of the mechanoelectrical feedback described in the heart. Furthermore, TREK-1 currents might contribute to the dysregulation of excitability in the heart in pathophysiological situations, such as those caused by abnormal stretch or ischaemia-associated cell swelling, thereby contributing to arrhythmogenesis. In this review, we focus on the functional role of TREK-1 in the heart and its putative contribution to cardiac mechanoelectrical coupling. Its cardiac expression among different species is discussed, alongside with functional evidence for TREK-1 currents in cardiomyocytes. In addition, evidence for the involvement of TREK-1 currents in different cardiac arrhythmias, such as atrial fibrillation or ventricular tachycardia, is summarized. Furthermore, the role of TREK-1 and its interaction partners in the regulation of the cardiac heart rate is reviewed. Finally, we focus on the significance of TREK-1 in the development of cardiac hypertrophy, cardiac fibrosis and heart failure.
TWIK 相关钾通道（TREK-1）双孔域钾（K）通道介导多种细胞的背景钾电流并调节细胞兴奋性。它们的功能活性受多种不同生理刺激的控制，如温度、细胞外或细胞内 pH 值、脂质和机械应激。通过将细胞兴奋性与机械应激联系起来，TREK-1 电流可能对介导心脏中描述的部分机械电反馈很重要。此外，TREK-1 电流可能在病理生理情况下（如异常拉伸或缺血相关细胞肿胀引起的情况）导致心脏兴奋性失调，从而导致心律失常发生。在这篇综述中，我们重点讨论了 TREK-1 在心脏中的功能作用及其对心脏机械电耦联的潜在贡献。讨论了不同物种中 TREK-1 的心脏表达，以及在心肌细胞中 TREK-1 电流的功能证据。此外，总结了 TREK-1 电流在不同心脏心律失常（如心房颤动或室性心动过速）中的作用。此外，还回顾了 TREK-1 及其相互作用伙伴在调节心脏心率中的作用。最后，我们重点讨论了 TREK-1 在心脏肥大、心脏纤维化和心力衰竭发展中的意义。
