Calcium leak induced sinus bradycardia

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, J_leak, was increased in sino-atrial node and ventricle model cells. The J_leak 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 v₂ values became 3.1×10^-5 m s^-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 J_leak 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.