Figure 8. The RyR2 LOF G4935R mutation has dominant negative effect on RyR2 WT.

HEK293 cells were transfected with RyR2 WT (A) or co-transfected with RyR2 WT and G4935R (B). Fluorescence intensity of the fluo-3-loaded transfected cells was monitored continuously before and after each caffeine addition. (C) Cumulative caffeine concentration–Ca²⁺ release relationships in HEK293 cells transfected with RyR2 WT or co-transfected with RyR2 WT/G4935R. Data shown are mean ± SEM (n=3). (D) [³H]ryanodine binding to cell lysates prepared from HEK293 cells transfected with RyR2 WT or the G4935R mutant or co-transfected with RyR2 WT/G4935R was carried out at various Ca²⁺ concentrations (0.1 nM to 100 µM). Data shown are mean ± SEM (n=5 separate experiments for WT, 3 for RyR2 WT/G4935R, and 4 for G4935R. *P <0.05 vs.WT.).