Figure 2: An allosteric model could explain a decrease in CDI.
From: Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca2+-dependent inactivation
(a) An allosteric CDI mechanism9,24. Ca2+ (black circles) binding to CaM (green) drives channels into mode Ca, which exhibits lower open probability (PO). (b) The model predicts two main components of CDI. FCDI (blue) is the fraction of channels in mode Ca (dependent on J(Ca2+) and thus PO) and CDImax (green) results from the relative ability of the channel to open once in mode Ca. The combination of these two curves defines the total CDI of a channel (black). (c) Mutations which inhibit channel opening (ΔΔGa>0) decrease Ca2+ entry, reducing FCDI (blue). These channels will exhibit lower CDI (black) due to a decreased ability to populate mode Ca. (d) Alternatively, enhanced channel opening (ΔΔGa<0), increases openings in mode Ca, thereby decreasing CDImax (green) and overall CDI (black).
