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Exercise training prevents Ca²⁺ dysregulation in coronary smooth muscle from diabetic dyslipidemic yucatan swine

Departments of ¹Medical Pharmacology and Physiology and ²Internal Medicine, and the Center for Diabetes & Cardiovascular Health, University of Missouri, Columbia, Missouri; ³Department of Molecular Physiology and Biological Physics, and the Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia; and ⁴Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana

Submitted 22 February 2006 ; accepted in final form 17 May 2006

Aerobic exercise training is known to have profound cardioprotective effects in disease, yet cellular mechanisms remain largely undefined. We tested the hypothesis that increased sarcoplasmic reticulum Ca²⁺ buffering and increased voltage-gated Ca²⁺ channel density underlie coronary smooth muscle intracellular Ca²⁺ (Ca²⁺_i) dysregulation in diabetic dyslipidemia and that exercise training would prevent these increases. Yucatan swine were maintained in 1) control, 2) alloxan-induced hyperglycemic, 3) high fat/cholesterol fed, 4) hyperglycemic plus high fat/cholesterol fed (diabetic dyslipidemic), and 5) diabetic dyslipidemic plus exercise-trained (treadmill running) conditions. After 20 wk, the heart was removed and smooth muscle cells isolated from the right coronary artery. We utilized fura-2 imaging of Ca²⁺_i levels to separate the functional role of the sarcoendoplasmic reticulum Ca²⁺-ATPase (SERCA) from the Na⁺-Ca²⁺ exchanger and the plasmalemmal Ca²⁺-ATPase, and whole-cell patch clamp to examine voltage-gated Ca²⁺ channel current density (i.e., Ca²⁺ influx). Results indicated that diabetic dyslipidemia impaired plasmalemmal Ca²⁺ efflux, increased basal Ca²⁺_i levels, increased SERCA protein and sarcoplasmic reticulum Ca²⁺_i buffering, and elicited an 50% decrease in voltage-gated Ca²⁺ channel current density. Exercise training concurrent with the diabetic dyslipidemic state restored plasmalemmal Ca²⁺ efflux, SERCA protein, sarcoplasmic reticulum Ca²⁺_i buffering, and voltage-gated Ca²⁺ channel current density to control levels. Interestingly, basal Ca²⁺_i levels were significantly lower in the exercise-trained group compared with control. Collectively, these results demonstrate a crucial role for exercise in the prevention of diabetic dyslipidemia-induced Ca²⁺_i dysregulation.

hypercholesterolemia; sarcoendoplasmic reticulum Ca²⁺-ATPase; voltage-gated Ca²⁺ channel; Na⁺-Ca²⁺ exchange; intracellular Ca²⁺ buffering; Ca²⁺ extrusion

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				Y. Yang, A. W. Jones, T. R. Thomas, and L. J. Rubin Influence of sex, high-fat diet, and exercise training on potassium currents of swine coronary smooth muscle Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1553 - H1563. [Abstract] [Full Text] [PDF]