Biophys J, August 2001, p. 614-629, Vol. 81, No. 2

Model Study of ATP and ADP Buffering, Transport of Ca²⁺ and Mg²⁺, and Regulation of Ion Pumps in Ventricular Myocyte

Anushka Michailova^* and Andrew McCulloch

 ^*Department of Biophysics, Bulgarian Academy of Science, Sofia, Bulgaria, and  Department of Bioengineering, University of California, San Diego, California 92093-0412 USA

We extended the model of the ventricular myocyte by Winslow et al. (Circ. Res. 1999, 84:571-586) by incorporating equations for Ca²⁺ and Mg²⁺ buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na⁺-K⁺ pump, sarcolemmal and sarcoplasmic Ca²⁺ pumps). The results indicate that, under normal conditions, Ca²⁺ binding by low-affinity ATP and diffusion of CaATP may affect the amplitude and time course of intracellular Ca²⁺ signals. The model also suggests that a fall in ATP/ADP ratio significantly reduces sarcoplasmic Ca²⁺ content, increases diastolic Ca²⁺, lowers systolic Ca²⁺, increases Ca²⁺ influx through L-type channels, and decreases the efficiency of the Na⁺/Ca²⁺ exchanger in extruding Ca²⁺ 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 Ca²⁺-ATPase pump by reduced diastolic MgATP levels. High Ca²⁺ concentrations developed near the membrane might have a greater influence on Mg²⁺, ATP, and ADP concentrations than that of the lower Ca²⁺ concentrations in the bulk myoplasm. The model predictions are in general agreement with experimental observations measured under normal and pathological conditions.

Biophys J, August 2001, p. 614-629, Vol. 81, No. 2
© 2001 by the Biophysical Society   0006-3495/01/08/614/16  $2.00

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