Two-Pore-Domain Potassium (K(2P)-) Channels: Cardiac Expression Patterns and Disease-Specific Remodelling Processes

Two-pore-domain potassium (K(2P)-) channels conduct outward K(+) currents that maintain the resting membrane potential and modulate action potential repolarization. Members of the K(2P) channel family are widely expressed among different human cell types and organs where they were shown to regulate important physiological processes. Their functional activity is controlled by a broad variety of different stimuli, like pH level, temperature, and mechanical stress but also by the presence of lipids or pharmacological agents. In patients suffering from cardiovascular diseases, alterations in K(2P)-channel expression and function have been observed, suggesting functional significance and a potential therapeutic role of these ion channels. For example, upregulation of atrial specific K(2P)3.1 (TASK-1) currents in atrial fibrillation (AF) patients was shown to contribute to atrial action potential duration shortening, a key feature of AF-associated atrial electrical remodelling. Therefore, targeting K(2P)3.1 (TASK-1) channels might constitute an intriguing strategy for AF treatment. Further, mechanoactive K(2P)2.1 (TREK-1) currents have been implicated in the development of cardiac hypertrophy, cardiac fibrosis and heart failure. Cardiovascular expression of other K(2P) channels has been described, functional evidence in cardiac tissue however remains sparse. In the present review, expression, function, and regulation of cardiovascular K(2P) channels are summarized and compared among different species. Remodelling patterns, observed in disease models are discussed and compared to findings from clinical patients to assess the therapeutic potential of K(2P) channels.