Mechanosensitive TREK-1 two-pore-domain potassium (K2P) channels in the cardiovascular system. (January 2021)

• Record Type: Journal Article
• Authors: Wiedmann, Felix; Rinné, Susanne; Donner, Birgit; Decher, Niels; Katus, Hugo A.; Schmidt, Constanze
• Is Part Of: Progress in biophysics and molecular biology. Volume 159(2021)
• Page Start: 126
• Page End: 135
• Publication Date: 2021-01
• Subjects: Arrhythmia -- K2P2.1 -- KCNK2 -- Mechanoelectrical feedback -- MEF -- TREK-1; Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2020.05.007
• Languages: English
• ISSNs: 0079-6107

Abstract

Abstract: TWIK-related K + channel (TREK-1) two-pore-domain potassium (K2P ) 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.