A novel mechanistic model is formulated for dynamic Ca2 +-dependent allosteric regulation of NCX1.
The NCX1 model is incorporated into both a super-resolution model of Ca2 + spark generation and a stochastic ventricular myocyte model.
Results in both models predict that Ca2 + spark frequency decreases with increasing dyad and/or peri-dyad NCX1 localization.
Whole-cell modeling results are quantitatively consistent with recent imaging data indicating t-tubule NCX1 localization levels.
NCX1 promotes Ca2 + entry across the sarcolemma into the dyad at depolarized Vm and in the presence of elevated local [Na+].