ASIC3 channel blockers bind ASIC3 trimer

Acid-sensing ion channels 1, 2, 3 and 5 (ASIC1, 2, 3 and 5, aka amiloride-sensitive cation channels) are a subfamily of the ENaC/Deg superfamily of ion channels. ASICs are low pH-activated Na+-permeable ion channels that are widely expressed in the central and peripheral nervous systems. ASICs act as pH sensors, leading to neuronal excitation when the pH drops. ASICs play important roles in mediating pain sensation in conditions such as stroke, inflammation, arthritis, cancer and migraine. They may additionally control the adverse behavioral and emotional symptoms of chronic pain such as anxiety and depression. ASIC3 channels are mainly expressed in the peripheral nervous system and inhibition of activity of these channels by ASIC3 channel blockers could be a promising tool for pain relief.<br><br>The diuretic amiloride, a nonspecific blocker of sodium channels, is a well-known drug that possesses a nonspecific inhibitory effect on ASICs (Ugawa et al. 2002).<br>

酸敏离子通道1、2、3和5（ASIC1、2、3和5，亦称咪唑啉敏感的阳离子通道）是ENaC/Deg超家族离子通道的一个亚家族。ASICs为低pH激活的钠离子通透性离子通道，在中央和周围神经系统中得到广泛表达。ASICs作为pH传感器，在pH值降低时导致神经元兴奋。ASICs在介导中风、炎症、关节炎、癌症和偏头痛等条件下的疼痛感觉中发挥着重要作用。它们还可能控制慢性疼痛的负面行为和情绪症状，如焦虑和抑郁。ASIC3通道主要在周围神经系统表达，通过ASIC3通道阻断剂对这些通道的活性进行抑制可能成为缓解疼痛的有前途的工具。<br><br>利尿剂咪唑啉，一种非特异性的钠通道阻断剂，是一种广为人知的药物，它对ASICs具有非特异性的抑制作用（Ugawa等，2002年）。