Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+. Export

@article{citeulike:688595, 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.}, address = {Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA. amihaylo@bioeng.ucsd.edu}, author = {Michailova, A. and Saucerman, J. and Belik, M. E. and McCulloch, A. D.}, citeulike-article-id = {688595}, citeulike-linkout-0 = {http://dx.doi.org/10.1529/biophysj.104.046284}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15738467}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15738467}, doi = {10.1529/biophysj.104.046284}, issn = {0006-3495}, journal = {Biophys J}, keywords = {ca, mg, release}, month = {March}, number = {3}, pages = {2234--2249}, posted-at = {2006-06-07 15:40:53}, priority = {2}, title = {Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+.}, url = {http://dx.doi.org/10.1529/biophysj.104.046284}, volume = {88}, year = {2005} }

TY - JOUR ID - citeulike:688595 L3 - citeulike-article-id:688595 N2 - 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. IS - 3 JF - Biophys J SN - 0006-3495 AD - Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA. amihaylo@bioeng.ucsd.edu EP - 2249 TI - Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+. VL - 88 SP - 2234 KW - ca KW - mg KW - release AU - Michailova, A AU - Saucerman, J AU - Belik, ME AU - McCulloch, AD PY - 2005/03// UR - http://dx.doi.org/10.1529/biophysj.104.046284 ER -