Effects of streptozotocin-induced diabetes on Kv channels in rat small coronary smooth muscle cells.
Diabetes impairs endothelium dependent vasodilation, but the mechanism of endothelium independent dilation is not well understood. In the present study, we examined the effect of streptozotocin (STZ)-induced diabetes on the vasomotor of small coronary artery and the activity of voltage-dependent K+ channel of vascular smooth muscle cells in STZ rats [corrected] using the videomicroscopy and patch clamp method. STZ-induced diabetes appeared to [corrected] reduce the vasodilation induced by beta-adrenoceptor agonist, isoproterenol (10(-9)-10(-5) mol/l), and adenylyl cyclase activator forskolin (10(-9)-10(-5) mol/l) respectively (isoproterenol: 44.2 +/- 6.7% vs. 82.5 +/- 4.8%, and forskolin: 54.4 +/- 4.5% vs. 94.3 +/- 2.4%). 4-AP, a Kv channel blocker of VSMC, further decreased dilation to isoproterenol (44.2 +/- 6.7% vs. 10.2 +/- 3.5%) and forskolin (54.4 +/- 4.5% vs. 13.8 +/- 11.0%) significantly. Whole cell K+ current recording demonstrated that STZ-induced diabetes decreased isoproterenol and forskolin-induced K+ current (ISO: 55.6 +/- 7.8 pA/pF vs. 28.4 +/- 3.4 pA/pF, forskolin: 61.3 +/- 9.8 pA/pF vs. 32.4 +/- 3.4 pA/pF). 4-AP further reduced the decreased K+ current (ISO: 28.4 +/- 3.4 pA/pF vs. 14.3 +/- 2.1 pA/pF, forskolin: 32.4 +/- 3.4 pA/pF vs. 14.8 +/- 2.9 pA/pF). These results indicated that STZ-induced diabetes impaired cAMP mediated dilation of small coronary artery and suppressed the Kv channel activity of vascular smooth muscle cells. Kv channel of VSMC was shown to play a determinate role reducing dilation of small coronary artery in STZ rats.
Chai
Qiang
Q
Institute of Physiology, School of Medicine, Shandong University, Jinan, Shandong Province, 250000, People's Republic of China.
Liu
Zhixiang
Z
Chen
Lianbi
L
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014664:Vasodilation / Q000187:drug effects
D024642:Potassium Channels, Voltage-Gated; D005576:Colforsin; D013311:Streptozocin; D015761:4-Aminopyridine; D007545:Isoproterenol