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Aims: Functional roles of calcium-activated potassium channels on the mechanical activity of epicardial coronary arteries obtained from a canine model of diabetes were investigated. Methods: Coronary arteries were isolated from healthy, alloxan-diabetic and insulin-treated diabetic dogs. Basal tensions, contractions induced by the prostaglandin (PG) analogue, U46619, and endothelium-dependent relaxations to acetylcholine (ACh) were modified with charybdotoxin (CHTX) + apamin (APA), inhibitors of calcium-activated potassium channels, as well as with Nω-nitro-l-arginine (LNA) + indomethacin (INDO) to suppress the synthesis of nitric oxide (NO) and PGs. The relaxing effect of nitroprusside-sodium (SNP), an NO donor, was also determined. Results: In diabetic coronary arteries, CHTX + APA did not change while LNA + INDO elevated the basal tension. PG-induced contractions were enhanced by CHTX + APA and by LNA + INDO in all the three groups of animals. CHTX + APA decreased the maximal relaxations to ACh in a partly insulin-dependent manner. LNA + INDO abolished the endothelium-dependent relaxations to ACh. In diabetic coronary arteries, the sensitivity to SNP-induced relaxation was enhanced, insulin independently, suggesting that NO could be partly responsible for maintaining intact ACh-induced vasorelaxation. Conclusion: In diabetic canine coronary artery, the vasomotor responses reflect up-regulation of calcium-activated potassium channels. This endothelial mechanism of the canine epicardial coronary artery may oppose vasoconstrictions in diabetic vascular tissue. [ABSTRACT FROM AUTHOR]

Aim: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. Methods: Diabetes was induced by a single injection of alloxan (145 mg kg−1 i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. Results: The QTc interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 ± 1.8 ms vs. 145 ± 2.8 ms, respectively, n = 9–10, P < 0.05). This QTc-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K+ current, IKs (from 1.48 ± 0.35 to 0.86 ± 0.17 pA pF−1 at +50 mV, n = 19–21, P < 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K+ current ( IK1), the rapid delayed rectifier K+ current ( IKr), the transient outward current ( Ito) and the L-type calcium current ( ICaL) between the control and alloxan-treated rabbits. Conclusion: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of IKs current, and thereby may enhance the risk of sudden cardiac death. [ABSTRACT FROM AUTHOR]