Exercise training attenuates coronary smooth muscle phenotypic modulation and nuclear Ca2+ signaling.
Physical inactivity is an independent risk factor for coronary heart disease, yet the mechanism(s) of exercise-related cardioprotection remains unknown. We tested the hypothesis that coronary smooth muscle after exercise training would have decreased mitogen-induced phenotypic modulation and enhanced regulation of nuclear Ca(2+). Yucatan swine were endurance exercise trained (EX) on a treadmill for 16-20 wk. EX reduced endothelin-1-induced DNA content by 40% compared with sedentary (SED) swine (P < 0.01). EX decreased single cell peak endothelin-1-induced cytosolic Ca(2+) responses compared with SED by 16% and peak nuclear Ca(2+) responses by 33% (P < 0.05), as determined by confocal microscopy. On the basis of these results, we hypothesized that sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and intracellular Ca(2+) stores in native smooth muscle are spatially localized to dissociate cytosolic Ca(2+) and nuclear Ca(2+). Subcellular localization of SERCA in living and fixed cells revealed a distribution of SERCA near the sarcolemma and on the nuclear envelope. These results show that EX enhances nuclear Ca(2+) regulation, possibly via SERCA, which may be one mechanism by which coronary smooth muscle cells from EX are less responsive to mitogen-induced phenotypic modulation.
Wamhoff
B R
BR
Department of Physiology, School of Medicine, University of Missouri, Columbia 65212, USA.
Bowles
D K
DK
Dietz
N J
NJ
Hu
Q
Q
Sturek
M
M
D000818:Animals; D001973:Bromodeoxyuridine; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002469:Cell Separation; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D010805:Physical Conditioning, Animal; D005082:Physical Exertion / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013556:Swine, Miniature
D019332:Endothelin-1; D005456:Fluorescent Dyes; D002110:Caffeine; D004247:DNA; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D001973:Bromodeoxyuridine; D002118:Calcium