Inactivation of Endothelial Small/Intermediate Conductance of Calcium-Activated Potassium Channels Contributes to Coronary Arteriolar Dysfunction in Diabetic Patients

Yuhong Liu, An Xie, Arun K. Singh, Afshin Ehsan, Gaurav Choudhary, Samuel Dudley, Frank W. Sellke, Jun Feng

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

BACKGROUND: Diabetes is associated with coronary arteriolar endothelial dysfunction. We investigated the role of the small/intermediate (SK(Ca)/IK(Ca)) conductance of calcium-activated potassium channels in diabetes-related endothelial dysfunction.

METHODS AND RESULTS: Coronary arterioles (80 to 150 μm in diameter) were dissected from discarded right atrial tissues of diabetic (glycosylated hemoglobin = 9.6±0.25) and nondiabetic patients (glycosylated hemoglobin 5.4±0.12) during coronary artery bypass graft surgery (n=8/group). In-vitro relaxation response of precontracted arterioles was examined in the presence of the selective SK(Ca)/IK(Ca) activator NS309 and other vasodilatory agents. The channel density and membrane potential of diabetic and nondiabetic endothelial cells was measured by using the whole cell patch-clamp technique. The protein expression and distribution of the SK(Ca)/IK(Ca) in the human myocardium and coronary arterioles was examined by Western blotting and immunohistochemistry. Our results indicate that diabetes significantly reduced the coronary arteriolar response to the SK(Ca)/IK(Ca) activator NS309 compared to the respective responses of nondiabetic vessels (P<0.05 versus nondiabetes). The relaxation response of diabetic arterioles to NS309 was prevented by denudation of endothelium (P=0.001 versus endothelium-intact). Diabetes significantly decreased endothelial SK(Ca)/IK(Ca) currents and hyperpolarization induced by the SK(Ca)/IK(Ca) activator NS309 as compared with that of nondiabetics. There were no significant differences in the expression and distribution of SK(Ca)/IK(Ca) proteins in the coronary microvessels.

CONCLUSIONS: Diabetes is associated with inactivation of endothelial SK(Ca)/IK(Ca) channels, which may contribute to endothelial dysfunction in diabetic patients.

Original languageEnglish (US)
Pages (from-to)e002062
JournalJournal of the American Heart Association
Volume4
Issue number8
DOIs
StatePublished - Aug 24 2015

Bibliographical note

Publisher Copyright:
© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Keywords

  • coronary microcirculation
  • coronary microvascular function
  • diabetes mellitus
  • potassium channels
  • vascular endothelial function

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