Fig. 11.

Effect of rate constants k_co and k_oc in the single channel RyR model (Eq. 1) on bulk SR [Ca²⁺] (A), fraction of open channels (B), spark frequency (C), and mean spark duration (D). *Standard parameters. Open diamonds indicate various changes in the open and closed dwell times of the RyR (cf. tetracaine, flecainide, and dual mechanism in Table 1 and Fig. 12). Open squares indicate that an increase in k_co was accompanied by a smaller decrease in k_oc corresponding to a low dose of caffeine. The steady-state SR load (c_sr) and fraction of open channels (f_O) are functions of the RyR Ca²⁺-binding constant K = k_oc/k_co, which was constant along the lines parallel to the diagonal band for which spark frequency and duration are well defined (dashed lines, score > 0.2).