Sarcoplasmic reticulum and contraction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K11306
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: Kyoto University
• Principal Investigator: Nishi Miyuki 京都大学, 薬学研究科, 研究員 (60183894)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: カルシウム / 小胞体

Outline of Final Research Achievements

Trimeric intracellular cation channels (TRIC-A and TRIC-B) are thought to provide counter-ion currents to enable charge-equilibration across the sarco/endoplasmic reticulum (SR) and nuclear membranes. We co-expressed TRIC-A or TRIC-B with RyR2 in HEK293 cells to examine if the presence of TRIC affects RyR2 function, and to characterise the permeability and gating properties of the TRIC channels. We found that both TRIC-A and TRIC-B altered the gating behaviour of RyR2 and its response to cytosolic Ca2+ but that TRIC-A exhibited a greater ability to stimulate the opening of RyR2. The reversal potentials of bilayers fused with high numbers of vesicles containing TRIC-A or TRIC-B, revealed both Cl- and K+ fluxes suggesting that TRIC channels are relatively non-selective ion channels. Our results indicate that the physiological roles of TRIC-A and TRIC-B may include direct, complementary regulation of RyR2 gating in addition to provision of counter-ion currents of both cations and anions.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

超高齢社会を反映して心機能に問題を抱える人は多く、心疾患は死因では第１位の悪性腫瘍についで第２位である。心臓の収縮を制御するのはカルシウムの規則正しい循環であり、その役割の１つを担っているのが小胞体からカルシウムを放出するリアノジン受容体である。従って、リアノジン受容体の研究は広く心臓研究者、臨床医の関心の的である。今回のリアノジン受容体とTRICの関係は全く新しい知見であり、閉塞感のあったリアノジン受容体研究の新たな展望で、治療につながれば社会的意義も計り知れない。