title: An increase in opening of BK(Ca) channels in smooth muscle cells in streptozotocin-induced diabetic mice.
abstract: OBJECTIVE
  To investigate the changes of function of large conductance of calcium-activated potassium channels (BK(Ca) channels) in thoracic aortic smooth muscle cells in early stage of streptozotocin (STZ)-induced diabetic C57BL/6J mice.
  
  
  METHODS
  Vascular muscle tension in the isolated thoracic aortic rings of mice was compared, and the role of BK(Ca) channels in relaxation of isolated mice thoracic aortic rings induced by acetylcholine (ACh) was determined. Meanwhile, single vascular smooth muscle cells (VSMCs) were isolated by collagenase, and BK(Ca) currents were recorded by patch-clamp single channel recording technique in symmetric high potassium solution.
  
  
  RESULTS
  Tetraethylammonium (TEA) 1 mmol/L, a selective calcium-activated potassium channel blocker, caused significant rightward shift in the concentration-response curves of ACh in the isolated thoracic aortic rings of diabetic mice and pD2 value of ACh-induced relaxation was decreased notably after TEA treatment [(6.3+/-0.4) vs (6.9+/-0.5), n=10 rings from 7 mice, P<0.01]. But pD2 value of ACh-induced relaxation in age-matched control mice did not change in presence and absence of TEA 1 mmol/L [(6.4+/-0.15) vs (6.5+/-0.5), n=7 rings from 6 mice, P>0.05]. Furthermore, conductance of BK(Ca) channels in single thoracic aortic smooth muscle cells was decreased [(199+/-15) pS, n=10 cells from 7 mice vs (266+/-11) pS, n=12 cells from 6 mice, P<0.01], but probability of open of BKCa channels was increased [(0.51+/-0.28) vs (0.11+/-0.06), n=6 cells from 6 mice, P<0.01], and the mean closed time in diabetic mice was reduced [(15+/-15) vs (132+/-98), n=6 cells from 6 mice, P<0.05].
  
  
  CONCLUSIONS
  The opening of BK(Ca) channels was increased in thoracic aortic smooth muscle cells in the early stage of STZ-induced diabetic C57BL/6J mice by reducing mean closed time, but the conductance of BK(Ca) channels was decreased.
authors.affiliation: Department of Pharmacology, Pharmacy College of Ji-nan University, Guangzhou 510632, China. YCL0412@163.net
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Ye
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.forename: Xian-Da
authors.initials: XD
authors.lastname: Ren
authors.forename: Rong-Jing
authors.initials: RJ
authors.lastname: Luo
authors.forename: Sheng-Yuan
authors.initials: SY
authors.lastname: Ding
authors.forename: Fu-Man
authors.initials: FM
authors.lastname: Yan
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Jiang
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology*
chemical_list: D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D019789:Tetraethylammonium; D000109:Acetylcholine