Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+ |
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| Authors: | Michailova Anushka Saucerman Jeffrey Belik Mary Ellen McCulloch Andrew D |
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| Affiliation: | Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA. amihaylo@bioeng.ucsd.edu |
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| Abstract: | ![]()
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. |
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| Keywords: | ATP, adenosine triphosphate ADP, adenosine diphosphate AP, action potential EC coupling, excitation-contraction coupling RyR, ryanodine receptor SERCA2a, SR Ca2+ ATPase SR, sarcoplasmic reticulum TnC, troponin C |
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