Potassium channel subfamily K member 10 (KCNK10) (KCNK10)

Potassium channel subfamily K member 10, commonly known as TREK-2, is a member of the two-pore domain potassium (K2P) channel family (UniProt P57471). It plays a critical role in setting and regulating the resting membrane potential of various cell types, particularly within the central and peripheral nervous systems. TREK-2 is polymodal, meaning it is activated by a diverse range of stimuli including mechanical stretch, heat, intracellular acidification, and polyunsaturated fatty acids (PubMed: 24790011). In the context of disease, TREK-2 is highly expressed in sensory neurons of the dorsal root ganglia, where it serves as a key regulator of pain signaling. Its activation is generally associated with analgesic effects, making it a promising target for chronic and neuropathic pain management (PubMed: 25344362). Furthermore, it has been implicated in neuroprotection during ischemic events and as a potential target for antidepressant therapies. Pharmacologically, TREK-2 is modulated by several clinical agents, including volatile anesthetics and certain antidepressants like fluoxetine, which acts as an inhibitor. This functional versatility makes it a significant target for drug development in neurology and pain management.

Other names

TREK-2TREK2Two pore domain potassium channel TREK-2K2P10.1TPKC1

Activation of TREK-2 channels promotes the efflux of potassium ions from the intracellular to the extracellular space, which leads to hyperpolarization of the cell membrane and a subsequent reduction in cellular excitability (IUPHAR/BPS Guide to Pharmacology, 2023). Conversely, inhibition of these channels results in membrane depolarization and increased neuronal firing. TREK-2 is a polymodal channel, meaning its gating is sensitive to various physical and chemical stimuli, including membrane stretch, temperature, and pH (UniProt P57471).