Referenced in: none

Automatically associated channels: Kv1.4 , Kv3.1 , Kv4.3

Title: Role of the calcium-independent transient outward current I(to1) in shaping action potential morphology and duration.

Authors: J L Greenstein, R Wu, S Po, G F Tomaselli, R L Winslow

Journal, date & volume: Circ. Res., 2000 Nov 24 , 87, 1026-33

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11090548

Abstract
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.