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.
- adenosine
- calcium
- cardiac,
- cardiovascular;
- cells,
- channel
- channels,
- computer
- contraction,
- cultured;
- diphosphate,
- gating,
- homeostasis,
- ion
- l-type,
- magnesium,
- metabolism;
- models,
- myocardial
- myocytes,
- physiology
- physiology;
- potassium
- signal
- signaling,
- simulation;
- transduction,
- triphosphate,
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