TWIK-related potassium channel (TREK) (TREK)

TWIK-related potassium channels (TREK), including TREK-1, TREK-2, and TRAAK, are members of the two-pore domain potassium (K2P) channel family that play a fundamental role in regulating the resting membrane potential and neuronal excitability [UniProt]. These channels are unique for their polymodal gating, as they are activated by a diverse array of stimuli including mechanical stretch, heat, intracellular acidification, and polyunsaturated fatty acids like arachidonic acid [PubMed: 25817450]. In the central nervous system, TREK channels act as inhibitory brakes on neuronal activity, and their dysfunction is linked to various neurological and psychiatric conditions such as major depressive disorder, chronic pain, and epilepsy [PubMed: 16691240]. TREK-1, in particular, has emerged as a promising target for rapidly acting antidepressants, as its inhibition mimics the effects of chronic SSRI treatment [PubMed: 20434928]. Furthermore, these channels are sensitive to volatile general anesthetics and neuroprotective agents like riluzole, highlighting their clinical relevance in anesthesia and stroke management [StatPearls]. Developing selective modulators for TREK channels remains a significant therapeutic goal, though challenges exist regarding tissue specificity and potential off-target effects in the cardiovascular system [PubMed: 28655116].

Other names

K2P channelTwo-pore domain potassium channelKCNK channelTREK-1TREK-2TRAAKKCNK2KCNK10KCNK4

Modulation of potassium efflux to regulate resting membrane potential and neuronal excitability; activators induce hyperpolarization while inhibitors induce depolarization [PubMed: 25817450].