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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/H1629    most recent 00466.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Borbouse, L. Articles by Tune, J. D. PubMed PubMed Citation Articles by Borbouse, L. Articles by Tune, J. D.

Impaired function of coronary BK_Ca channels in metabolic syndrome

¹Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; ²Department of Exercise Physiology, Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, West Virginia; ³Department of Biomedical Sciences, University of Missouri, Columbia, Missouri; and ⁴Department of Integrative Medical Sciences, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio

Submitted May 20, 2009 ; accepted in final form August 25, 2009

The role of large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels in regulation of coronary microvascular function is widely appreciated, but molecular and functional changes underlying the deleterious influence of metabolic syndrome (MetS) have not been determined. Male Ossabaw miniature swine consumed for 3–6 mo a normal diet (11% kcal from fat) or an excess-calorie atherogenic diet that induces MetS (45% kcal from fat, 2% cholesterol, 20% kcal from fructose). MetS significantly impaired coronary vasodilation to the BK_Ca opener NS-1619 in vivo (30–100 µg) and reduced the contribution of these channels to adenosine-induced microvascular vasodilation in vitro (1–100 µM). MetS reduced whole cell penitrem A (1 µM)-sensitive K⁺ current and NS-1619-activated (10 µM) current in isolated coronary vascular smooth muscle cells. MetS increased the concentration of free intracellular Ca²⁺ and augmented coronary vasoconstriction to the L-type Ca²⁺ channel agonist BAY K 8644 (10 pM–10 nM). BK_Ca channel and β₁ protein expression was increased in coronary arteries from MetS swine. Coronary vascular dysfunction in MetS is related to impaired BK_Ca channel function and is accompanied by significant increases in L-type Ca²⁺ channel-mediated coronary vasoconstriction.

blood flow; circulation; ion channels; obesity

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				N. J. Rusch BK channels in cardiovascular disease: a complex story of channel dysregulation Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1580 - H1582. [Full Text] [PDF]