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Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyteWe 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.
Document ID
20040112355
Document Type
Reprint (Version printed in journal)
Authors
Michailova, A.
(Bulgarian Academy of Science Sofia, Bulgaria)
McCulloch, A.
Date Acquired
August 21, 2013
Publication Date
August 1, 2001
Publication Information
Publication: Biophysical journal
Volume: 81
Issue: 2
ISSN: 0006-3495
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: P41 RR08605
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Cardiopulmonary
Non-NASA Center
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