Simulations predict a bimodal relationship between I(Kv4.3) density and action potential duration, where perturbations may produce either prolongation or shortening depending on baseline levels.
Computational modeling reveals a bimodal relationship between I_to1 density and action potential duration, highlighting complex coupling with L-type calcium currents.
The Kv4.3-encoded current (I:(Kv4.3)) has been identified as the major component of the voltage-dependent Ca(2+)-independent transient outward current (I:(to1)) in human and canine ventricular cells. Experimental evidence supports a correlation between I:(to1) density and prominence of the phase 1 notch; however, the role of I:(to1) in modulating action potential duration (APD) remains unclear. To help resolve this role, Markov state models of the human and canine Kv4.3- and Kv1.4-encoded currents at 35 degrees C are developed on the basis of experimental measurements. A model of canine I:(to1) is formulated as the combination of these Kv4.3 and Kv1.4 currents and is incorporated into an existing canine ventricular myocyte model. Simulations demonstrate strong coupling between L-type Ca(2+) current and I:(Kv4.3) and predict a bimodal relationship between I:(Kv4.3) density and APD whereby perturbations in I:(Kv4.3) density may produce either prolongation or shortening of APD, depending on baseline I:(to1) current level.
Greenstein et al. (Fri,) conducted a other in Action potential morphology and duration in ventricular cells. Perturbations in I(Kv4.3) density vs. Baseline I(to1) current level was evaluated on Action potential duration (APD). Simulations predict a bimodal relationship between I(Kv4.3) density and action potential duration, where perturbations may produce either prolongation or shortening depending on baseline levels.