Mathie Alistair, Veale Emma L
The Universities of Kent and Greenwich at Medway, Medway School of Pharmacy, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
Curr Opin Investig Drugs. 2007 Jul;8(7):555-62.
Two-pore domain potassium (K2P) channels are expressed in cells throughout the body and give rise to leak potassium currents which control the excitability of these cells. Although not inhibited by classical potassium channel-blocking drugs, such as tetraethylammonium and 4-aminopyridine, K2P channels are regulated by a diverse array of pharmacological mediators. There are six main families of K2P channels and among these certain members of the TREK family (ie, TREK-1 and TREK-2) are activated by general anesthetic agents such as halothane, xenon and nitrous oxide. In addition, all members of the TREK familyare activated by neuroprotective agents, such as riluzole, polyunsaturated fatty acids and lysophospholipids, suggesting that these channels play an important role in neuroprotection. TREK channels are also inhibited by chlorpromazine, local anesthetics and the antidepressant fluoxetine. Furthermore, all members of the TASK family are inhibited by cannabinoids and local anesthetics, and TASK-3 is selectively inhibited by ruthenium red. Thus, the diversity and physiological importance of K2P channels suggest that the development of selective compounds to target these proteins has therapeutic potential for CNS disorders such as stroke, depression and epilepsy.
双孔结构域钾离子（K2P）通道在全身细胞中均有表达，并产生钾离子渗漏电流，该电流控制着这些细胞的兴奋性。尽管K2P通道不受经典钾离子通道阻断药物（如四乙铵和4-氨基吡啶）的抑制，但它们受多种药理介质的调节。K2P通道有六个主要家族，其中TREK家族的某些成员（即TREK-1和TREK-2）可被氟烷、氙气和一氧化二氮等全身麻醉剂激活。此外，TREK家族的所有成员均可被神经保护剂（如利鲁唑、多不饱和脂肪酸和溶血磷脂）激活，这表明这些通道在神经保护中发挥着重要作用。TREK通道也可被氯丙嗪、局部麻醉剂和抗抑郁药氟西汀抑制。此外，TASK家族的所有成员均可被大麻素和局部麻醉剂抑制，而TASK-3可被钌红选择性抑制。因此，K2P通道的多样性和生理重要性表明，开发针对这些蛋白质的选择性化合物对中风、抑郁症和癫痫等中枢神经系统疾病具有治疗潜力。
