Identification of regulatory factors for TMEM16A calcium-activated chloride channel

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460104
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: YAMAMURA Hisao 名古屋市立大学, 薬学研究科(研究院), 准教授 (80398362)
• Co-Investigator(Renkei-kenkyūsha): IMAIZUMI Yuji 名古屋市立大学, 大学院薬学研究科, 教授 (60117794)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: クロライドチャネル / カルシウム / TMEM16 / 血管 / 平滑筋 / 門脈 / 門脈圧亢進症 / イオンチャネル

Outline of Final Research Achievements

The calcium-activated chloride (ClCa) channel plays substantial roles in the regulation of membrane excitability in vascular smooth muscles. Recently, TMEM16A-coding protein has been identified as the molecular entity responsible for ClCa channel in several types of vascular smooth muscles. In this study, the functional expression of TMEM16A and its regulatory factors was examined in murine portal vein smooth muscle cells. TMEM16A was abundantly expressed in portal vein myocytes and formed a dimeric ClCa channel. The activity of TMEM16A ClCa channel was modified by the interaction with actin cytoskeleton. TMEM16A was also interacted with TMEM16B to form a heteromeric ClCa channel. Finally, TMEM16A was downregulated in portal vein smooth muscle cells from hepatic cirrhosis-induced portal hypertensive mice. These results provide useful information for elucidating physiological and pathological significances of TMEM16A ClCa channels in vascular smooth muscles.

Free Research Field

薬理学