Alterations of TMEM16a allostery in human retinal microarterioles in long-standing hypertension

作者：Gui, Dongmei^*; Li, Yanfeng; Chen, Xiaolong

来源：IUBMB Life, 2015, 67(5): 348-354.

DOI：10.1002/iub.1376

• calcium-activated chloride channels
• vascular resistance
• retinal ischemia
• chronic hypertension

We hypothesized that the calcium-activated chloride channel (CACC) transmembrane member 16A (TMEM16A) ionic mechanism may be a general mechanism in remodeling of vascular smooth muscles, including the retina. These vascular remodeling may have a critical impact on retinal ischemia during chronic hypertension. In this study, we examined TMEM16A protein interactions with calmodulin and CaMKII likely cause efflux of chloride, thus resulting in increased vascular resistance by increasing vascular wall tone in long-standing hypertension. Control experiments were performed in static concentrations of calcium and using the specific TMEM16A inhibitor T16Ainh-A01 [2-[(5-ethyl-1,6-dihydro-4-methyl-6-oxo-2-pyrimidinyl)thio]-N-[4-(4-methoxyphenyl)-2-thia zolyl]acetamide]. The results of our study provide preliminary evidence that CACC shows altered pharmacologic and biochemical properties in retinal vessel in long-standing hypertension.

• 出版日期2015-5
• 单位中国医科大学; 辽宁省人民医院