Molecular Background of Leak K+Currents: Two-Pore Domain Potassium Channels

Abstract

Two-pore domain K+(K2P) channels give rise to leak (also called background) K+currents. The well-known role of background K+currents is to stabilize the negative resting membrane potential and counterbalance depolarization. However, it has become apparent in the past decade (during the detailed examination of the cloned and corresponding native K2Pchannel types) that this primary hyperpolarizing action is not performed passively. The K2Pchannels are regulated by a wide variety of voltage-independent factors. Basic physicochemical parameters (e.g., pH, temperature, membrane stretch) and also several intracellular signaling pathways substantially and specifically modulate the different members of the six K2Pchannel subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). The deep implication in diverse physiological processes, the circumscribed expression pattern of the different channels, and the interesting pharmacological profile brought the K2Pchannel family into the spotlight. In this review, we focus on the physiological roles of K2Pchannels in the most extensively investigated cell types, with special emphasis on the molecular mechanisms of channel regulation.