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

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38 Scopus citations

Abstract

Background-—Diabetes is associated with coronary arteriolar endothelial dysfunction. We investigated the role of the small/ intermediate (SKCa /IKCa) conductance of calcium-activated potassium channels in diabetes-related endothelial dysfunction. Methods and Results-—Coronary arterioles (80 to 150 lm 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 SKCa/IKCa 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 SKCa /IKCa 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 SKCa /IKCa 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 SKCa /IKCa currents and hyperpolarization induced by the SKCa /IKCa activator NS309 as compared with that of nondiabetics. There were no significant differences in the expression and distribution of SKCa /IKCa proteins in the coronary microvessels. Conclusions-—Diabetes is associated with inactivation of endothelial SKCa /IKCa channels, which may contribute to endothelial dysfunction in diabetic patients.

Original languageEnglish (US)
Article numbere002062
JournalJournal of the American Heart Association
Volume4
Issue number8
DOIs
StatePublished - 2015

Bibliographical note

Funding Information:
This research project was supported by Rhode Island Foundation RIF-20123834 (Feng), NIGMS/NIH grant (pilot project) 1P20GM103652 (Feng), AHA-Grant-in-Aid 15GRNT 25710105 (Feng), and supported in part by the National Heart, Lung, and Blood Institute HL-46716 (Sellke).

Publisher Copyright:
© 2015 The Authors.

Keywords

  • Coronary microcirculation
  • Coronary microvascular function
  • Diabetes mellitus
  • Potassium channels
  • Vascular endothelial function

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