Integrative study on arrhythmogenicity associated with adaptive and pathological remodeling of stressed hearts.

2014 Fiscal Year Final Research Report

• Project Area: Establishment of Integrative Multi-level Systems Biology and its Applications
• Project/Area Number: 22136008
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: Fukuoka University
• Principal Investigator: INOUE Ryuji 福岡大学, 医学部, 教授 (30232573)
• Co-Investigator(Kenkyū-buntansha): IRIBE Gentaro 岡山大学, 医歯薬学総合研究科, 講師 (90284885) ; NAKAYA Michio 九州大学, 薬学研究科, 准教授 (80464387)
• Co-Investigator(Renkei-kenkyūsha): MATSUOKA Satoshi 福井大学, 医学部, 教授 (00263096)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 不整脈 / 心ストレス / 心リモデリング / TRP蛋白質 / Caハンドリング異常 / 遺伝子変異 / PIP2ダイナミクス / イオンチャネル

Outline of Final Research Achievements

The present study aimed at exploring novel pathogenic mechanisms underlying abnormal excitability and arrhythmic changes in stressed hearts. For this purpose, we focused on stress-responsive Ca2+/Na+ channel molecules transient receptor potential (TRP) proteins, and investigated their pathological significance by combining both experimental and theoretical approaches. The results clearly indicate that post-remodeling upregulation as well as small differences in PIP2 sensitivity among highly homologous isoforms and arrhythmic mutations could account for part of their notably different functionalities, leading to enhanced risk of arrhythmias and abnormal excitability. This integrative approaches of experiments and numerical model-based simulations may provide a useful framework to design/develop new anti-arrhythmic drugs targeting TRP channels and simultaneously facilitate our understanding about an otherwise elusive complexity of cardiac excitation/propagation and its disorders.

Free Research Field

TRPチャネルの分子病態生理学