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Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+.
- Source :
-
Biophysical journal [Biophys J] 2005 Mar; Vol. 88 (3), pp. 2234-49. - Publication Year :
- 2005
-
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.
- Subjects :
- Cells, Cultured
Computer Simulation
Homeostasis physiology
Ion Channel Gating physiology
Myocardial Contraction physiology
Signal Transduction physiology
Adenosine Diphosphate metabolism
Adenosine Triphosphate metabolism
Calcium Channels, L-Type physiology
Calcium Signaling physiology
Magnesium metabolism
Models, Cardiovascular
Myocytes, Cardiac physiology
Potassium Channels physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3495
- Volume :
- 88
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biophysical journal
- Publication Type :
- Academic Journal
- Accession number :
- 15738467
- Full Text :
- https://doi.org/10.1529/biophysj.104.046284