Fig. 8.

Effects of 90% K⁺ channel inhibition and 100% increase in IP₃ production at t = 100 s on [Ca]_cyt (nM), [Ca]_md (nM), and [Ca]_SR (×10² mM), with the separate-store model. Note that the [Ca]_md peak is off-scale. Phase A: RyR-mediated Ca²⁺-induced Ca²⁺ release (CICR) in microdomains, sharp [Ca]_md ascent. Subsequent depletion of RyR stores and filling up of IP₃R stores. Rapid membrane depolarization and repolarization, [Ca]_cyt peak. Phase B: activation of NCX current, sharp [Ca]_md descent. Ca²⁺ content in RyR and IP₃R stores reaches minima and maxima. Phase C: slower [Ca]_md descent. Subsequent replenishment of RyR stores and depletion of IP₃R stores as I_RyR^md and I_IP3R^md-SERCA decrease. Phase D: slowly rising RyR- and IP₃R-mediated Ca²⁺ release into microdomains, progressive [Ca]_md increase. Stabilized Ca²⁺ concentration in cytosol and SR stores.