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Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+Changes in cytosolic free Mg(2+) and adenosine nucleotide phosphates affect cardiac excitability and contractility. To investigate how modulation by Mg(2+), ATP, and ADP of K(ATP) and L-type Ca(2+) channels influences excitation-contraction coupling, we incorporated equations for intracellular ATP and MgADP regulation of the K(ATP) current and MgATP regulation of the L-type Ca(2+) current in an ionic-metabolic model of the canine ventricular myocyte. The new model: 1), quantitatively reproduces a dose-response relationship for the effects of changes in ATP on K(ATP) current, 2), simulates effects of ADP in modulating ATP sensitivity of K(ATP) channel, 3), predicts activation of Ca(2+) current during rapid increase in MgATP, and 4), demonstrates that decreased ATP/ADP ratio with normal total Mg(2+) or increased free Mg(2+) with normal ATP and ADP activate K(ATP) current, shorten action potential, and alter ionic currents and intracellular Ca(2+) signals. The model predictions are in agreement with experimental data measured under normal and a variety of pathological conditions.
Document ID
20050194229
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Michailova, Anushka
(University of California San Diego La Jolla, CA 92093, United States)
Saucerman, Jeffrey
Belik, Mary Ellen
McCulloch, Andrew D.
Date Acquired
August 23, 2013
Publication Date
March 1, 2005
Publication Information
Publication: Biophysical journal
Volume: 88
Issue: 3
ISSN: 0006-3495
Subject Category
Life Sciences (General)
Distribution Limits
Public
Copyright
Other
Keywords
Validation Studies
NASA Discipline Cardiopulmonary
Non-NASA Center
Evaluation Studies

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