Elucidation of regulatory mechanisms of type 2 ryanodine receptors by introducing artificial amino acids

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Juntendo University
• Principal Investigator: MURAYAMA Takashi 順天堂大学, 医学部, 准教授 (10230012)
• Co-Investigator(Renkei-kenkyūsha): KUREBAYASHI Nagomi 順天堂大学, 医学部, 准教授 (50133335) ; SAKAMOTO Kensaku 理化学研究所, 拡張遺伝暗号システム研究チーム, チームリーダー (50240685) ; OBA Toshiharu 中部大学, 応用生物学部, 教授 (50008330)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: リアノジン受容体 / 筋小胞体 / カルシウムチャネル / 相互作用 / 人工アミノ酸

Outline of Final Research Achievements

Type 2 ryanodine receptor is a Ca2+ release channel in the sarcoplasmic reticulum and plays an important role in excitation-contraction coupling in heart. Mutations in RyR2 cause hyperactivate the channel, leading to arrhythmogenic diseases. Here, we examined molecular mechanism of disease-cuasing mutations on the channel activity by determining the properties of the mutant channels. Furthermore, we tried to detect possible interactions within or between subdomains by introducing photo-crosslinkable artificial amino acids. We found that disease-causing mutations affect various parameters of the channel activity. Possible alterations of interactions within the domains are also suggested.

Free Research Field

薬理学