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Am J Physiol Heart Circ Physiol 281: H223-H231, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 1, H223-H231, July 2001

Sarcoplasmic reticulum Ca2+ uptake is impaired in coronary smooth muscle distal to coronary occlusion

Cristine L. Heaps1,2, Michael Sturek2,4, Elmer M. Price1,3, M. Harold Laughlin1,2,3, and Janet L. Parker1,2,5

1 Dalton Cardiovascular Research Center and Departments of 2 Physiology, 3 Veterinary Biomedical Sciences, and 4 Internal Medicine, University of Missouri, Columbia, Missouri 65211; and 5 Department of Medical Physiology, Texas A&M University, College Station, Texas 77843

After chronic occlusion, collateral-dependent coronary arteries exhibit alterations in both vasomotor reactivity and associated myoplasmic free Ca2+ levels that are prevented by chronic exercise training. We tested the hypotheses that coronary occlusion diminishes Ca2+ uptake by the sarcoplasmic reticulum (SR) and that exercise training would prevent impaired SR Ca2+ uptake. Ameroid constrictors were surgically placed around the proximal left circumflex (LCx) artery of female swine 8 wk before initiating 16-wk sedentary (pen confined) or exercise-training (treadmill run) protocols. Twenty-four weeks after Ameroid placement, smooth muscles cells were enzymatically dissociated from both the LCx and nonoccluded left anterior descending (LAD) arteries of sedentary and exercise-trained pigs, and myoplasmic free Ca2+ was studied using fura 2 microfluorometry. After the SR Ca2+ store was partially depleted with caffeine (5 mM), KCl-induced membrane depolarization produced a significant decrease in the time to half-maximal (t1/2) myoplasmic free Ca2+ accumulation in LCx versus LAD cells of sedentary pigs. Furthermore, inhibition of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA; 10 µM cyclopiazonic acid) significantly reduced t1/2 in cells isolated from the LAD but not from the LCx. Exercise training did not prevent the differences in t1/2 myoplasmic free Ca2+ accumulation observed between LCx and LAD cells. Occlusion or exercise training did not alter SERCA protein levels. These results support our hypothesis of impaired SR Ca2+ uptake in coronary smooth muscle cells isolated distal to chronic occlusion. Impaired SR Ca2+ uptake was independent of SERCA protein levels and was not prevented by exercise training.

vascular smooth muscle; calcium; SERCA; exercise training; porcine


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