Interplay of Ryanodine Receptor Distribution and Calcium Dynamics

Spontaneously generated calcium (Ca 2+) waves can trigger arrhythmias in ventricular and atrial myocytes. Yet, Ca 2+ waves also serve the physiological function of mediating global Ca 2+ increase and muscle contraction in atrial myocytes. We examine the factors that influence Ca 2+ wave initiation by mathematical modeling and large-scale computational (supercomputer) simulations. An important finding is the existence of a strong coupling between the ryanodine receptor distribution and Ca 2+ dynamics. Even modest changes in the ryanodine receptor spacing profoundly affect the probability of Ca 2+ wave initiation. As a consequence of this finding, we suggest that there is information flow from the contractile system to the Ca 2+ control system and this dynamical interplay could contribute to the increased incidence of arrhythmias during heart failure.