Potassium channel subfamily K member 2 (TREK-1) (TREK-1)

TREK-1 (Potassium channel subfamily K member 2) is a member of the two-pore-domain potassium (K2P) channel family that serves as a fundamental "leak" channel, setting and stabilizing the resting membrane potential [1, 3]. It is characterized by its polymodal gating, responding to diverse physical and chemical cues such as membrane stretch, temperature, intracellular pH, and polyunsaturated fatty acids like arachidonic acid [5, 13]. TREK-1 is widely expressed throughout the central nervous system and cardiovascular system, where it plays a pivotal role in controlling neuronal and muscular excitability [1, 10]. In disease contexts, TREK-1 is a significant target for treating depression, as its inhibition by drugs like SSRIs or the peptide spadin leads to antidepressant-like effects [1, 13]. Furthermore, its activation is explored for neuroprotection in stroke and epilepsy, as well as for managing chronic pain and pulmonary arterial hypertension [2, 11, 14]. The channel's unique sensitivity to volatile anesthetics makes it a critical mediator of general anesthesia [2, 15]. However, its broad expression across the heart, brain, and smooth muscles presents therapeutic challenges, including potential risks for cardiac arrhythmias and altered sensitivity to anesthetic agents [10, 12].

Other names

KCNK2K2P2.1TPKC1TREKTREK1hTREK-1chTREK-1ePotassium two pore domain channel subfamily K member 2

Activation of TREK-1 opens background potassium channels, causing K+ efflux and membrane hyperpolarization, which reduces neuronal and muscular excitability. Inhibition leads to membrane depolarization and increased excitability, which is utilized in antidepressant therapy.