Impaired function of coronary BKCa channels in metabolic syndrome

Léna Borbouse, Gregory M. Dick, Shinichi Asano, Shawn B. Bender, U. Deniz Dincer, Gregory A. Payne, Zachary P. Neeb, Ian N. Bratz, Michael Sturek, Johnathan D. Tune

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The role of large-conductance Ca2+-activated K+ (BKCa) 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 BKCa 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). BKCa channel α and β1 protein expression was increased in coronary arteries from MetS swine. Coronary vascular dysfunction in MetS is related to impaired BKCa channel function and is accompanied by significant increases in L-type Ca2+ channel-mediated coronary vasoconstriction.

Original languageEnglish (US)
Pages (from-to)H1629-H1637
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number5
DOIs
StatePublished - Nov 1 2009

Keywords

  • Blood flow
  • Circulation
  • Ion channels
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Impaired function of coronary BK<sub>Ca</sub> channels in metabolic syndrome'. Together they form a unique fingerprint.

  • Cite this

    Borbouse, L., Dick, G. M., Asano, S., Bender, S. B., Dincer, U. D., Payne, G. A., Neeb, Z. P., Bratz, I. N., Sturek, M., & Tune, J. D. (2009). Impaired function of coronary BKCa channels in metabolic syndrome. American Journal of Physiology - Heart and Circulatory Physiology, 297(5), H1629-H1637. https://doi.org/10.1152/ajpheart.00466.2009