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.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Liu Y,Xie A,Singh AK,Ehsan A,Choudhary G,Dudley S,Sellke FW,Feng Jdoi
10.1161/JAHA.115.002062subject
Has Abstractpub_date
2015-08-24 00:00:00pages
e002062issue
8issn
2047-9980pii
JAHA.115.002062journal_volume
4pub_type
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