Peña Fernando, Ordaz Benito
Departamento de Farmacobiología, Cinvestav-Sede Sur, Calz. de los Tenorios 235, Col. Granjas Coapa, 14330, México, D.F., Mexico.
Mini Rev Med Chem. 2008 Jul;8(8):812-9. doi: 10.2174/138955708784912166.
Non-selective cationic channels (NSCC) are a heterogeneous family of channels, widely expressed in non-excitable and excitable cells, that share several functional characteristics but have diverse molecular origin. NSCC can be formed by transient receptor potential (TRP) channels, calcium activated non-selective channels, hyperpolarization activated cation currents, acid-sensitive cationic channels (ASIC), etc. As a result of its wide expression, as well as to the fact that the activation of such currents produce a persistent membrane depolarization, NSCC have been involved in a variety of neuronal processes such as signal transduction, firing pattern (including plateau potentials and bursting mechanisms) as well as synaptic transmission. Due to the relevance of such channels, alterations in their normal function have been associated with the pathophysiology of several nervous system diseases. Over the last years several blockers of such channels have been discovered. Here we review the pharmacology of NSCC blockers including trivalent cations, verapamil derivates, flufenamic acid, the "typical" TRP blockers 2-APB, ACA and SKF 96365 as well as ASIC blockers. This review focuses on the pharmacological properties of such drugs and their potential use for the understanding of the nervous system as well as for the treatment of neurological diseases.
非选择性阳离子通道（NSCC）是一类异质性通道家族，广泛表达于非兴奋性细胞和兴奋性细胞中，它们具有一些共同的功能特征，但分子起源各不相同。NSCC可由瞬时受体电位（TRP）通道、钙激活非选择性通道、超极化激活阳离子电流、酸敏感阳离子通道（ASIC）等形成。由于其广泛表达，以及此类电流的激活会产生持续的膜去极化这一事实，NSCC参与了多种神经元过程，如信号转导、放电模式（包括平台电位和爆发机制）以及突触传递。由于此类通道的重要性，其正常功能的改变与多种神经系统疾病的病理生理学相关。在过去几年中，已发现了几种此类通道的阻滞剂。在此，我们综述NSCC阻滞剂的药理学，包括三价阳离子、维拉帕米衍生物、氟芬那酸、“典型”的TRP阻滞剂2-APB、ACA和SKF 96365以及ASIC阻滞剂。本综述重点关注此类药物的药理学特性及其在理解神经系统以及治疗神经疾病方面的潜在用途。
