Background Rapid pacing rates induce alternations in the cytosolic calcium concentration caused by fluctuations in calcium rele However, the relationship between calcium alternans and refractoriness of the SR calcium release channel (RyR2) Methodology/Principal Findings To investigate how ryanodine receptor (RyR2) refractoriness modulates calcium handling on a beat-to-beat basis u used a mathematical rabbit cardiomyocyte model to study the beat-to-beat calcium response as a function of RyR were constructed depicting the beat-to-beat response. When alternans was observed, a novel numerical clamping was caused by oscillations in SR calcium loading or by RyR2 refractoriness. Using this protocol, we identified regio loading or RyR2 refractoriness underlie the induction of calcium alternans, and we found that at the onset of altern inactivation rates of the RyR2, calcium alternans was caused by alternation in SR calcium loading, while at low act level of available RyR2s. Conclusions/Significance We have mapped cardiomyocyte beat-to-beat responses as a function of RyR2 activation and inactivation, identify refractoriness underlie the induction of calcium alternans. A corollary of this work is that RyR2 refractoriness due t of calcium alternans even when alternation in SR calcium load is present.

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