Key result
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.
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Greenstein et al. (2000) studied 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.
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