Figure 13. Model simulation of release-dependent inactivation (RDI) under specific conditions.

A, with the SR function removed, RDI did not occur under Na⁺-free conditions, indicating that Na⁺–Ca²⁺ exchange (Incx) had virtually no role in the absence of an active SR. B, with an active SR, the RDI in the absence of Na⁺ (inactive Incx) is greater than that under physiological conditions (active Incx). Top, depiction of the voltage pulse train given to the L-type Ca²⁺ channels (ICaLs), with varying times between the pre-pulse and test pulse. Middle (B), simulated [Ca²⁺] in the junctional subsarcolemmal space. Bottom, simulated ICaL currents resulting from the voltage pulses. The traces from separate simulations are overlapped to show the trends. Red lines are the experimental results from control ICaL current amplitude measurements during RDI.