Altered L-type Ca(2+) channel currents in vascular smooth muscle cells from experimental diabetic rats.
Vascular complications of diabetes are associated with abnormal Ca(2+) handling by vascular smooth muscle cells (SMCs) in which the alteration in L-type voltage-dependent Ca(2+) channel (VDCC) currents may play an important role. In the present study, the characteristics of L-type VDCC currents in tail artery SMCs from streptozotocin-induced diabetic rats were examined. The densities, but not the voltage dependence, of L-type VDCC currents were reduced as diabetes progressed from 1 wk to 3 mo. The inhibitory effect of dibutyryl-cAMP on L-type VDCC currents was greater in diabetic SMCs than in age-matched control cells (P < 0.01). Both the stimulatory effect of BAY K 8644 and the inhibitory effect of nifedipine on L-type VDCC currents were significantly enhanced in diabetic cells. The diabetes-related abnormalities in L-type VDCC currents were mimicked by culturing SMCs with a high concentration of glucose. Our results suggest that the properties of L-type VDCC in diabetic vascular SMCs were significantly altered, partially related to the increased L-type VDCC sensitivity to cAMP and hyperglycemia.
Wang
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Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada. wangrui@duke.usask.ca
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000503:physiopathology; D003994:Bucladesine / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004095:Dihydropyridines / Q000494:pharmacology; D004553:Electric Conductivity; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000098:blood supply
D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D003994:Bucladesine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D000242:Cyclic AMP; D005947:Glucose