TWIK-related potassium channel (TWIK)

TWIK-related potassium channels are a family of two-pore domain potassium channels (K2P channels), characterized by four transmembrane domains and two pore-forming domains per subunit, forming a functional channel from two subunits. Members include TWIK, TREK, TASK, TRAAK, TALK, and TRESK channels, each with unique tissue distribution and functional regulation. These channels are essential for setting resting membrane potential, regulating cellular excitability, and participating in neurophysiological processes. Mutations or dysfunctions are implicated in migraine (especially TRESK), cardiac arrhythmias, pain processing, and disease states involving altered membrane excitability. While pharmacological targeting is challenging due to a lack of specificity and the need for selective modulators, ongoing research explores therapeutic potentials, particularly in neurology and cardiology.

Other names

Two-pore domain potassium channels (K2P channels)Tandem pore domain potassium channelsTWIK channelTREK channel (TWIK-related K+ channel)TASK channel (TWIK-related acid-sensitive K+ channel)TRAAK channel (TWIK-related arachidonic acid stimulated K+ channel)TRESK channel (TWIK-related spinal cord K+ channel)

Channel agonism/activation (increased K+ current, e.g., by BL-1249 and polyunsaturated fatty acids); Channel inhibition/blockade (e.g., by A1899); Indirect modulation by signaling molecules or second messengers (physiological regulation)