© 2000 American Heart Association, Inc.
Cellular Biology |
Role of the Calcium-Independent Transient Outward Current Ito1 in Shaping Action Potential Morphology and Duration
From the Department of Biomedical Engineering, Whitaker Biomedical Engineering Institute (J.L.G., R.L.W.), the Center for Computational Medicine & Biology (J.L.G., R.L.W.), the Section of Molecular and Cellular Cardiology, Division of Cardiology, Department of Medicine (R.W., S.P., G.F.T.), and the Institute for Molecular Cardiobiology (R.W., S.P., G.F.T., R.L.W.), Johns Hopkins University School of Medicine, Baltimore, Md.
Correspondence to Raimond L. Winslow, PhD, Room 411, Traylor Research Building, 720 Rutland Ave, Baltimore, MD 21205. E-mail rwinslow{at}bme.jhu.edu
Abstract—The Kv4.3-encoded current (IKv4.3) has been identified as the major component of the voltage-dependent Ca2+-independent transient outward current (Ito1) in human and canine ventricular cells. Experimental evidence supports a correlation between Ito1 density and prominence of the phase 1 notch; however, the role of Ito1 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 Ito1 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 IKv4.3 and predict a bimodal relationship between IKv4.3 density and APD whereby perturbations in IKv4.3 density may produce either prolongation or shortening of APD, depending on baseline Ito1 current level.
Key Words: K+ channel • transient outward current • ventricular action potential • action potential duration
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