Potassium channel subfamily K member 10 (TREK-2) (TREK-2)

Potassium channel subfamily K member 10, commonly known as TREK-2, is a two-pore-domain potassium (K2P) channel that plays a critical role in maintaining the resting membrane potential and regulating cellular excitability [3, 6]. It is highly expressed in the sensory neurons of the dorsal root and trigeminal ganglia, where it acts as a "brake" on neuronal firing by allowing the outward leak of potassium ions [5, 12]. TREK-2 is uniquely polymodal, responding to diverse physiological stimuli such as mechanical stretch, heat, intracellular acidosis, and polyunsaturated fatty acids [6, 13]. Its ability to modulate nociceptor sensitivity makes it a promising therapeutic target for the treatment of chronic, neuropathic, and postoperative pain [8, 11]. Beyond its role in somatosensation, TREK-2 has been implicated in the regulation of the cell cycle and proliferation in certain cancers, such as bladder carcinoma [9]. Pharmacologically, the channel is activated by certain bioactive lipids like 11-deoxy prostaglandin F2α and inhibited by several classes of antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants [7, 10]. However, the development of TREK-2-specific therapies is complicated by its high structural homology with other K2P channels like TREK-1 and TRAAK, which can lead to off-target effects [5, 8].

Other names

KCNK10K2p10.1TREK2PPP1R97TWIK-related K+ channel 2Outward rectifying potassium channel protein TREK-2

TREK-2 acts as a background potassium leak channel. Drugs that activate TREK-2 increase the outward flow of potassium ions, which hyperpolarizes the cell membrane and reduces neuronal excitability, providing an analgesic effect. Conversely, inhibitors of TREK-2 reduce potassium conductance, which can lead to membrane depolarization and increased excitability or altered cell cycle progression.