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, 13403] were expressed in HEK293 cells to assess their Ca²⁺ dependence in [³H]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 [³H]ryanodine binding affinity while maintaining channel activity.