AJP - Heart and Circulatory Physiology, Vol 257, Issue 3 942-H953, Copyright © 1989 by American Physiological Society
Tension and electrolyte changes with Na+-K+ pump inhibition in rat papillary muscle
D. Parsons, K. P. Burton, H. K. Hagler, J. T. Willerson and L. M. Buja
Department of Pathology, University of Texas, Southwestern Medical School, Dallas 75235-9072.
Myocardial ischemic injury results in altered membrane integrity, energy
depletion, and electrolyte shifts leading to accumulation of intracellular
Ca. However, analysis of the direct effects of Ca accumulation is
complicated by other concomitant cellular changes produced by ischemia. The
purpose of this study was to examine the effects of Ca loading in rat
papillary muscles produced by Na+-K+ pump inhibition in oxygenated K+-free
buffer. Changes in contractile characteristics, high energy phosphate, and
elemental concentrations of subcellular compartments were measured.
Electron probe X-ray microanalysis was used to assess elemental
concentrations in cryosections. After 3 h of Na+-K+ pump inhibition,
resting tension (RT) increased to 164% and developed tension (DT) fell to
16.8% of control values. One hour after return to complete buffer, RT and
DT partially recovered but remained significantly different from the 180 to
240-min values for the control muscles. Electron probe X-ray microanalysis
showed increases in cytoplasmic and mitochondrial Na and Ca and a decrease
in K during Na+-K+ pump inhibition. Mitochondrial Ca was greater than
100-fold greater than Ca in control mitochondria. Morphologically, the
majority of cells showed ultrastructural damage. The mean ATP level was 20%
of control. After 1 h of recovery, the cells appeared more heterogeneous,
and the mean mitochondrial Ca decreased, whereas mean cytoplasmic Ca
increased. Further statistical analysis showed a bimodal distribution for
Na, Ca, K, Mg, and Cl, which coincided with the morphologically mixed
population of cells. This suggests that replacement of extracellular K+ was
associated with restored electrolyte gradients in some cells and the
persistent or further alteration of electrolytes in others. These results
suggest that variable Ca accumulation and associated ATP depletion without
the compounding effects of ischemia lead to cell injury similar to
reperfusion injury reported in ischemic myocardium.
