Effect of RyR2 refractoriness and hypercalcemia on calcium overload, spontaneous release, and calcium alternans

In this work we use a computer model of a ventricular rabbit myocyte to study several factors that affect sarcoplasmic reticulum (SR) calcium load, such as hypercalcemia, SR calcium buffering, or ryanodine receptor (RyR2) dynamics. General conditions for the appearance of calcium spontaneous release in situations with calcium overload are obtained. Furthermore, we study the appearance of alternans under these conditions. The presence of calcium alternans may be due to either a steep calcium load release relation, resulting in oscillations in SR Ca content, or to a slow recovery from refractoriness of the RyR2. We find that a change in calsequestrin buffering dynamics or extracellular calcium concentration greatly affects the appearance of the former type of alternans, but not of the latter.