title: Sarcoplasmic reticulum Ca(2+) uptake is impaired in coronary smooth muscle distal to coronary occlusion.
abstract: After chronic occlusion, collateral-dependent coronary arteries exhibit alterations in both vasomotor reactivity and associated myoplasmic free Ca(2+) levels that are prevented by chronic exercise training. We tested the hypotheses that coronary occlusion diminishes Ca(2+) uptake by the sarcoplasmic reticulum (SR) and that exercise training would prevent impaired SR Ca(2+) 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 Ca(2+) was studied using fura 2 microfluorometry. After the SR Ca(2+) store was partially depleted with caffeine (5 mM), KCl-induced membrane depolarization produced a significant decrease in the time to half-maximal (t(1/2)) myoplasmic free Ca(2+) accumulation in LCx versus LAD cells of sedentary pigs. Furthermore, inhibition of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA; 10 microM cyclopiazonic acid) significantly reduced t(1/2) in cells isolated from the LAD but not from the LCx. Exercise training did not prevent the differences in t(1/2) myoplasmic free Ca(2+) 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 Ca(2+) uptake in coronary smooth muscle cells isolated distal to chronic occlusion. Impaired SR Ca(2+) uptake was independent of SERCA protein levels and was not prevented by exercise training.
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211, USA. heapsc@missouri.edu
authors.forename: C L
authors.initials: CL
authors.lastname: Heaps
authors.forename: M
authors.initials: M
authors.lastname: Sturek
authors.forename: E M
authors.initials: EM
authors.lastname: Price
authors.forename: M H
authors.initials: MH
authors.lastname: Laughlin
authors.forename: J L
authors.initials: JL
authors.lastname: Parker
mesh_terms: D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D003331:Coronary Vessels / Q000378:metabolism* / Q000503:physiopathology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D007211:Indoles / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D009210:Myofibrils / Q000378:metabolism; D010805:Physical Conditioning, Animal; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013552:Swine; D013556:Swine, Miniature
chemical_list: D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007211:Indoles; D001464:Barium; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2; C000543:cyclopiazonic acid