Fig. 4.

Effects of external KCl elevation on microdomain and cytosolic Ca²⁺ currents as a function of time (in s), using the separate-store model. At t = 120 s, [K]_out is raised from 5.4 to 100 mM. A: IP₃R current is low because of its inhibition by [Ca]_md elevation while RyR current is large because of [Ca]_md-mediated stimulation. B: [Ca]_md elevation stimulates both IP₃R store- and RyR store-sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) pumps facing the microdomains to the point that they become saturated. NCX, Na⁺/Ca²⁺ exchanger. C: the increase in IP₃R-SR store Ca²⁺ leads to reversal of pumping by IP₃R-SERCA that face the cytosol (negative values mean flux from the SR to the cytosol). The RyR-SERCA facing the cytosol take up Ca²⁺ from the cytosol into the RyR-SR store. D: the large increase in [Ca]_SR-IP3R leads to elevation of Ca²⁺ current through those IP₃R that face the cytosol, and the rise in [Ca]_cyt stimulates elevation of current through the RyR that face the cytosol.