Two-pore domain potassium channel TWIK-1 (KCNK1) (TWIK-1, KCNK1)

Two-pore domain potassium channel TWIK-1 (KCNK1) is a dimeric ion channel that plays a fundamental role in maintaining the resting membrane potential of cells by conducting potassium ions across the plasma membrane. Structurally unique among potassium channels, TWIK-1 consists of two subunits each containing four transmembrane domains and two pore-forming loops, which together form a single ion conduction pathway. The channel produces background leak currents that are quasi-instantaneous, noninactivating, and active across all membrane potentials, making it insensitive to classical potassium channel blockers. TWIK-1 is predominantly expressed in the central nervous system and has a well-established role in regulating cardiac rhythm and atrial size. The channel is regulated by diverse stimuli including protein kinase C activation, pH changes, and G-protein signaling. Dysregulation of TWIK-1 and related K2P channels has been associated with cardiac arrhythmias and heart failure, suggesting the channel represents a potential therapeutic target for cardiovascular diseases.

Other names

K2P1TWIK1

For drugs targeting K2P channels generally: Activation of channel opening leads to K+ efflux and hyperpolarization of the cell membrane, reducing cell excitability. Inhibition of channel activity increases membrane potential depolarization.