Conformation of Cav1.2 channel in the inactivated state by calmodulin binding

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Kagoshima University
• Principal Investigator: Minobe Etsuko 鹿児島大学, 医歯学域医学系, 講師 (00448581)
• Research Collaborator: Mori Masayuki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: カルシウムチャネル / カルモジュリン / パッチクランプ法 / inside-out / Cav1.2 / カルシウムイオン / run-down / ATP

Outline of Final Research Achievements

Activity of Cav1.2 channels requires calmodulin (CaM). Conformation of the channel-CaM complex has been reported, but they are still in debate. We have investigated the conformation of Cav1.2 channel in the inactivated state by recording the activity of carboxyl-terminal (CT) deletion channel linked to CaM (CaM-linked channel), W82A-CaM-linked channel and amino-terminal (NT) deletion CaM-linked channel (delN-CaM-linked channel), using the patch-clamp technique. The CaM-linked channel showed both Ca2+ and CaM dependent inactivation, while the W82A-CaM-linked channel and the delN-CaM-linked channel showed only CaM-dependent inactivation but not Ca2+-dependent inactivation. These results suggest that the inactivation induced by one CaM linked with channel may require the NT of the channel, while more than one CaM induced inactivation may take place without NT, but within CT of the channel. Thus, there might be two types of conformation of Ca2+-dependent inactivation of Cav1.2.

Free Research Field

電気生理学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

Cav1.2チャネルを含むL型Ca2+チャネルは、心筋、骨格筋、神経系や分泌細胞に分布し、筋収縮、遺伝子発現、シナプス伝達、ホルモン分泌などにおいて重要な役割をもつため、本研究により得られた知見を広く応用できる。また、カルモジュリンの遺伝子異常から病態につながる例も報告されており、カルモジュリンによるチャネルの活性調節は重要な位置づけにある。