Role of Ca2+-dependent Cl- current on delayed afterdepolarizations. A simulation study.
Calcium-dependent chloride current (I (Cl,Ca)) is the second component (I (to2)) of the transient outward current (I (to)) that provokes the action potential (AP) phase 1 repolarization. This current contributes to the transient inward current (I (ti)) that generates delayed afterdepolarizations (DAD) in several pathological conditions. The present work uses a computer AP model of rabbit atrial myocyte and a one-dimensional (1D) tissue model of 400 cells to study the role of I (Cl,Ca) on the generation of DAD and triggered activity under calcium-overload conditions. A mathematical model describing the dependence of I (Cl,Ca) on intracellular Ca(2+) is proposed. This model takes into account the experimentally recorded characteristics of I (Cl,Ca): (1) calcium dependence, (2) voltage-dependent inactivation, and (3) I-V field-diffusion relation. Our results support the hypothesis that I (Cl,Ca) plays an important role in action potential repolarization, mainly at high frequencies. In the calcium-overload conditions tested in this work, I (Cl,Ca) represents between 28% and 44% of the total I (ti) that provokes DADs. Our simulations also show that the blockage of I (Cl,Ca) reduces the calcium overload range in which DADs provoke triggered activity.
Gomis-Tena
Julio
J
Instituto de Investigación e Innovación en Bioingeniería, Universidad Politécnica de Valencia, Camino de Vera s/n, Valencia 46022, Spain.
Saiz
Javier
J
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D016275:Atrial Function / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology; D002713:Chlorine / Q000378:metabolism*; D003198:Computer Simulation; D006329:Heart Conduction System / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology*; D011817:Rabbits
D018118:Chloride Channels; D002713:Chlorine; D002118:Calcium