Abstract
We extended the model of the ventricular myocyte by Winslow et al.
(Circ. Res 1999, 84:571-586) by incorporating equations for Ca(2+)
and Mg(2+) buffering and transport by ATP and ADP and equations for
MgATP regulation of ion transporters (Na(+)-K(+) pump, sarcolemmal
and sarcoplasmic Ca(2+) pumps). The results indicate that, under
normal conditions, Ca(2+) binding by low-affinity ATP and diffusion
of CaATP may affect the amplitude and time course of intracellular
Ca(2+) signals. The model also suggests that a fall in ATP/ADP ratio
significantly reduces sarcoplasmic Ca(2+) content, increases diastolic
Ca(2+), lowers systolic Ca(2+), increases Ca(2+) influx through L-type
channels, and decreases the efficiency of the Na(+)/Ca(2+) exchanger
in extruding Ca(2+) during periodic voltage-clamp stimulation. The
analysis suggests that the most important reason for these changes
during metabolic inhibition is the down-regulation of the sarcoplasmic
Ca(2+)-ATPase pump by reduced diastolic MgATP levels. High Ca(2+)
concentrations developed near the membrane might have a greater influence
on Mg(2+), ATP, and ADP concentrations than that of the lower Ca(2+)
concentrations in the bulk myoplasm. The model predictions are in
general agreement with experimental observations measured under normal
and pathological conditions.
- adenosine
- biological;
- buffers;
- calcium,
- cells,
- conductivity;
- cultured;
- cytology/metabolism;
- diphosphate,
- electric
- ion
- kinetics;
- magnesium,
- metabolism
- metabolism;
- models,
- myocardium,
- patch-clamp
- potassium,
- pumps,
- sodium,
- techniques;
- transport;
- triphosphate,
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