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

Carol A. Witczak, Brian R. Wamhoff, Michael Sturek

Research output: Contribution to journalArticle

25 Scopus citations


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 Ca 2+-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 Ca 2+ 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.

Original languageEnglish (US)
Pages (from-to)752-762
Number of pages11
JournalJournal of Applied Physiology
Issue number3
StatePublished - Sep 14 2006


  • Ca extrusion
  • Hypercholesterolemia
  • Intracellular Ca buffering
  • Na-Ca exchange
  • Sarcoendoplasmic reticulum Ca-ATPase
  • Voltage-gated Ca channel

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Fingerprint Dive into the research topics of 'Exercise training prevents Ca<sup>2+</sup> dysregulation in coronary smooth muscle from diabetic dyslipidemic yucatan swine'. Together they form a unique fingerprint.

  • Cite this