The Role of Calsequestrin, Triadin, and Junctin in Conferring Cardiac Ryanodine Receptor Responsiveness to Luminal Calcium

摘要: The level of Ca inside the sarcoplasmic reticulum (SR) is an important determinant functional activity release channel/ryanodine receptor (RyR) in cardiac muscle. However, molecular basis RyR regulation by luminal remains largely unknown. In present study, we investigated potential role SR auxiliary proteins calsequestrin (CSQ), triadin 1, and junctin forming calcium sensor for RyR. Recordings single channels incorporated into lipid bilayers, from either vesicle or purified preparations, were performed presence MgATP using Cs+ as charge carrier. Raising [Ca] 20 μM to 5 mM increased open channel probability (Po) native RyRs vesicles, but not RyRs. Adding CSQ side produced no significant changes Po, nor did it restore ability respond Ca. When 1 added channels, Po significantly; however, still remained unresponsive [Ca]. reassociated with junctin, adding a decrease activity. After reassociation all three proteins, responded rises increasing their Po. These results suggest that complex CSQ, confer sensitivity. apparently serves inhibits at low [Ca], whereas and/or may be required mediate interactions