Cl-通过Cl-通道的流入和流出在调节生物功能的稳态中起作用。因此,Cl-通道的功能亢进或功能障碍引起病理机制。Cl-通道超家族包括电压门控Cl-(ClC)通道,Ca2+激活Cl-通道(ClCa;TMEM16A/TMEM16B),囊性纤维化跨膜传导调节通道,和配体门控Cl-通道。这些通道普遍表达以调节离子稳态,肌肉紧张,膜兴奋性,细胞体积,生存,神经传递,和跨上皮运输。Cl-通道的激活或抑制改变了膜电位,从而影响细胞溶质Ca2+信号。细胞溶质[Ca2+]的升高引发大多数细胞的生理和病理反应。然而,Cl-通道的作用尚未像阳离子(Na+,Ca2+,和K+)频道。我们最近报道了:(i)门静脉和肺动脉平滑肌细胞(PASMC)中TMEM16A/ClCa通道的功能表达,松果体细胞,和脑毛细血管内皮细胞;(ii)松果体细胞中的TMEM16B/ClCa通道;(iii)PASMC和软骨细胞中的ClC-3通道;和(iv)软骨细胞中的ClC-7通道。我们还表明,TMEM16A和ClC-7通道表达下调与肝硬化门脉高压和骨关节炎有关,分别,而TMEM16A和ClC-3通道的表达增强参与了脑缺血和肺动脉高压的发病机制,分别。对Cl-通道的生理/病理功能的进一步研究将提供对生物学功能的见解并有助于筛选相关疾病的药物发现的新靶标。
Cl- influx and efflux through Cl- channels play a role in regulating the homeostasis of biological functions. Therefore, the hyperfunction or dysfunction of Cl- channels elicits pathological mechanisms. The Cl- channel superfamily includes voltage-gated Cl- (ClC) channels, Ca2+-activated Cl- channels (ClCa; TMEM16A/TMEM16B), cystic fibrosis transmembrane conductance regulator channels, and ligand-gated Cl- channels. These channels are ubiquitously expressed to regulate ion homeostasis, muscle tonus, membrane excitability, cell volume, survival, neurotransmission, and transepithelial transport. The activation or inhibition of Cl- channels changes the membrane potential, thereby affecting cytosolic Ca2+ signals. An elevation in cytosolic [Ca2+] triggers physiological and pathological responses in most cells. However, the roles of Cl- channels have not yet been examined as extensively as cation (Na+, Ca2+, and K+) channels. We recently reported the functional expression of: (i) TMEM16A/ClCa channels in portal vein and pulmonary arterial smooth muscle cells (PASMC), pinealocytes, and brain capillary endothelial cells; (ii) TMEM16B/ClCa channels in pinealocytes; (iii) ClC-3 channels in PASMC and chondrocytes; and (iv) ClC-7 channels in chondrocytes. We also showed that the down-regulation of TMEM16A and ClC-7 channel expression was associated with cirrhotic portal hypertension and osteoarthritis, respectively, whereas the enhanced expression of TMEM16A and ClC-3 channels was involved in the pathogenesis of cerebral ischemia and pulmonary arterial hypertension, respectively. Further investigations on the physiological/pathological functions of Cl- channels will provide insights into biological functions and contribute to the screening of novel target(s) of drug discovery for associated diseases.