Activation and deactivation of couplons determined by the positive-feedback mechanism. (A) AP. (B) [Ca2+]SRrl. (C) [Ca2+]nd (CaLR, CaL0, Ca0R, and Ca00). The dotted curves of CaLR, CaL0, and Ca0R indicate that they are theoretical values and have virtually no influence on the kinetics, since both the couplon and LCC are mostly closed during this period. (D) The overall activation rate ( ) and deactivation rate ( ) of the couplon and were obtained after fixing [Ca2+]SRrl to a control value. (E) pO(t) (= Yooo + Ycoo + Yoco + Ycco, red), and pOeq and pOLCC (Yooo + Yooc; the peak is off the scale). The two vertical lines in all panels indicate the onset and offset of the stimulus current pulse. Inset A shows the reduced two-state transition of a couplon. Inset B shows the feedback loop formed by the five time-dependent variables, connected by five red arrows with equation numbers. The thick red and blue arrows indicate each Ca2+ release flux, which directly increases or decreases [Ca2+]jnc or [Ca2+]SRrl, respectively.