Potassium channel subfamily K member 2 (KCNK2) (K2P2.1)

K2P2.1, also known as TREK-1 (TWIK-related K+ channel 1), is a member of the two-pore-domain potassium (K2P) channel family encoded by the KCNK2 gene (guidetopharmacology.org). Unlike voltage-gated channels, K2P2.1 functions as a leak channel that remains open at resting membrane potentials, thereby playing a critical role in setting the resting potential and regulating cellular excitability (nih.gov). It is highly sensitive to a variety of physiological and pharmacological stimuli, including mechanical stretch, temperature, pH, and bioactive lipids like arachidonic acid (frontiersin.org). In the central nervous system, K2P2.1 is involved in neuroprotection, pain perception, and mood regulation, making it a significant target for antidepressants and analgesics (cellphysiolbiochem.com). Beyond the brain, it is expressed in the heart and lungs, where it influences cardiac rhythm and inflammatory responses (nih.gov). Pharmacological modulators include the neuroprotective drug riluzole and volatile anesthetics, which activate the channel, as well as the antidepressant fluoxetine and the peptide spadin, which act as inhibitors (frontiersin.org). The channel's unique structure, featuring two pore-forming loops per subunit, allows it to integrate multiple signaling pathways to fine-tune the electrical state of the cell (wikipedia.org). Research into K2P2.1 has highlighted its potential in treating conditions ranging from major depressive disorder to acute respiratory distress syndrome (nih.gov).

Other names

TREK-1KCNK2TREKTPKC1TWIK-related K+ channel 1

Activation or inhibition of potassium ion efflux through the selectivity filter gate (C-type gate) to regulate membrane potential and cellular excitability (acs.org, nih.gov).