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

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. © 2015 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.