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

Joseph L. Greenstein, Richard Wu, Sunny Po, Gordon F. Tomaselli, Raimond L. Winslow

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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 languageEnglish (US)
Pages (from-to)1026-1033
Number of pages8
JournalCirculation research
Volume87
Issue number11
DOIs
StatePublished - Nov 24 2000

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Keywords

  • Action potential duration
  • K channel
  • Transient outward current
  • Ventricular action potential

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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