Evidence for a role of C-terminus in Ca2+ inactivation of skeletal muscle Ca2+ release channel (ryanodine receptor)

Six chimeras of the skeletal muscle (RyR1) and cardiac muscle (RyR2) Ca2+ release channels (ryanodine receptors) previously used to identify RyR1 dihydropyridine receptor interactions [Nakai et al, (1998) J, Biol, Chem, 273, 13303] were expressed in HEK293 cells to assess their Ca2+ dependence in [H-3]ryanodine binding and single channel measurements. The results indicate that the C-terminal one-fourth has a major role in Ca2+ activation and inactivation of RyR1. Further, our results show that replacement of RyR1 regions with corresponding RyR2 regions can result in loss and/or reduction of [H-3]ryanodine binding affinity while maintaining channel activity.