Figure 9.

Schematic model of RyR regulation via interdomain interaction. A basal interaction between the cytoplasmic N-terminus of RyR2 and transmembrane C-terminus is mediated by amino acids 3722-4610 (I-domain) and suppresses aberrant Ca²⁺ release via the Ca²⁺-channel pore. Caffeine activation triggers a conformational reorganization within the I-domain of the RyR polypeptide which results in increased FRET signal between dsRed and eGFP fusion partners (i.e., increased proximity of the fluorophores), and is associated with increased Ca²⁺ release through the RyR channel (see Figures 5 and 6).