Progress in understanding the central nervous system pharmacology of the two-pore domain potassium channel TREK-1

Two-pore domain potassium channels (K₂P) make up a subfamily of potassium channels discovered in the 1990s, and TREK-1 is the most widely studied subtype of K₂P. TREK-1 is widely expressed in the body and especially in the central nervous system, where its main role is to control cell excitability and maintain the membrane potential below the depolarization threshold. It thereby participates in regulating various physiological and pathological processes. TREK-1 is also a potential drug target in many diseases. It is known that many marketed drugs can affect the function of TREK-1, but currently there are no specific TREK-1 modulators or drugs. We review the structure, distribution and regulation of TREK-1 and focus on recent progress in understanding the pharmacology of TREK-1 and its role in neuroprotection, depression, anesthesia and epilepsy. The research status of TREK-1 modulators is discussed.