Abstract
The Kv4.3-encoded current (I(Kv4.3)) has been identified as the major component of the voltage-dependent Ca2+-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°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 Ca2+ 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.
Original language | English (US) |
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Pages (from-to) | 1026-1033 |
Number of pages | 8 |
Journal | Circulation research |
Volume | 87 |
Issue number | 11 |
DOIs | |
State | Published - Nov 24 2000 |
Externally published | Yes |
Keywords
- Action potential duration
- K channel
- Transient outward current
- Ventricular action potential
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine