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 v
₂
, the calcium leak rate constant from the net sarcoplasmic reticulum. In the sino-atrial node cell model, the pacing cycle length increased steadily till v
₂
values became 3.1×10
^-5
m s
^-1
. Further increase of v
₂
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
⁺
/Ca
²⁺
exchanger current were decreased when v
₂
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.