Downregulation of TMEM16A Calcium-Activated Chloride Channel Contributes to Cerebrovascular Remodeling During Hypertension by Promoting Basilar Smooth Muscle Cell Proliferation

The Ca(2+)-activated chloride channel (CaCC) plays an important role in a variety of physiological functions. In vascular smooth muscle cells, CaCC is involved in the regulation of agonist-stimulated contraction and myogenic tone. The physiological functions of CaCC in blood vessels are not fully re...

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Veröffentlicht in:	Circulation (New York, N.Y.) N.Y.), 2012-02, Vol.125 (5), p.697-707
Hauptverfasser:	MI WANG, HUI YANG, GUAN, Yong-Yuan, ZHENG, Ling-Yun, ZHENG ZHANG, TANG, Yong-Bo, WANG, Guan-Lei, DU, Yan-Hua, LV, Xiao-Fei, JIE LIU, ZHOU, Jia-Guo
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Anoctamin-1 Basilar Artery - metabolism Basilar Artery - pathology Bestrophins Biological and medical sciences Blood and lymphatic vessels Blood vessels and receptors Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism Cardiology. Vascular system Cell Cycle - physiology Cell Proliferation Cells, Cultured Chloride Channels - metabolism Disease Models, Animal Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Down-Regulation Fundamental and applied biological sciences. Psychology Hypertension - metabolism Hypertension - pathology Male Medical sciences Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - pathology Patch-Clamp Techniques Rats Rats, Inbred SHR Rats, Inbred WKY Rats, Sprague-Dawley Vertebrates: cardiovascular system
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Zusammenfassung:	The Ca(2+)-activated chloride channel (CaCC) plays an important role in a variety of physiological functions. In vascular smooth muscle cells, CaCC is involved in the regulation of agonist-stimulated contraction and myogenic tone. The physiological functions of CaCC in blood vessels are not fully revealed because of the lack of specific channel blockers and the uncertainty concerning its molecular identity. Whole-cell patch-clamp studies showed that knockdown of TMEM16A but not bestrophin-3 attenuated CaCC currents in rat basilar smooth muscle cells. The activity of CaCC in basilar smooth muscle cells isolated from 2-kidney, 2-clip renohypertensive rats was decreased, and CaCC activity was negatively correlated with blood pressure (n=25; P
ISSN:	0009-7322 1524-4539
DOI:	10.1161/circulationaha.111.041806