Bradycardia is found to be a complication during catecholaminergic polymorphic ventricular tachycardia in which calcium leak plays a pivotal role. In this computational study, we determined the effects of sarcoplasmic reticulum calcium leak on sino-atrial node and ventricular model cells function. A sarcoplasmic reticulum calcium leak current, Jleak, was increased in sino-atrial node and ventricle model cells. The Jleak current is determined by v2, the calcium leak rate constant from the net sarcoplasmic reticulum. In the sino-atrial node cell model, the pacing cycle length increased steadily till v2values became 3.1??10???5 ms???1. Further increase of v2 made pacemaking give rise to long-short, big amplitude-small amplitude oscillations as well as arrest. The amplitude of subspace calcium, calcium diffusion, maximum upstroke velocity of the membrane potential, L-type calcium current and Na+/Ca2+ exchanger current were decreased when v2 was increased in sino-atrial node cell model. However, the effects of Jleak on ventricular action potential and ionic currents are small. The results show the significance of calcium leak as a major mechanism of sino-atrial node dysfunction.
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