瞬时受体电位M2型离子通道配体及功能研究进展

Advances in function and ligands of transient receptor potential melastain 2 channels

瞬时受体电位M2型(transient receptor potential melastain 2,TRPM2)离子通道作为配体门控的非选择性阳离子通道,在大脑中分布广泛,主要介导Na^+和Ca^(2+)等阳离子内流,使细胞去极化、胞内Ca^(2+)浓度升高,进而参与细胞相关的病理生理过程。高Ca^(2+)浓度或氧化应激等因素直接或间接作用下胞内生成的大量腺苷二磷酸核糖(adenosine diphosphate ribose,ADPR)与TRPM2通道的NUDT9-H结构域结合,从而激活TRPM2通道。虽然TRPM2介导许多病理过程,但是现有的TRPM2通道的拮抗剂尚缺乏特异性,因此通过寻找和研究其特异性拮抗剂有望使TRPM2通道成为诸多相关疾病的潜在治疗靶点。

As nonselective cation channels,transient receptor potential melastain 2(TRPM2)channels are widely distributed in the brain,mainly mediate the inflow of Na^+and Ca^2+,leading to cell depolarization and the increasement of intracellular concentration of Ca^2+,which are involved in many physiological and pathophysiological processes.Due to increased calcium concentration or oxidative stress,channel gating is induced by either direct or indirect formation of adenosine diphosphate ribose(ADPR)that binds to a NUDT9 homology domain(NUDT9-H)in the channel.There is no specific TRPM2 antagonist so far.Considering some pathological processes are mediated by TRPM2 channels,the study and discovery of specific TRPM2 blockers might contribute to the effective treatment of many related diseases.