An increase in opening of BK(Ca) channels in smooth muscle cells in streptozotocin-induced diabetic mice.
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.
Ye
Chun-Lin
CL
Department of Pharmacology, Pharmacy College of Ji-nan University, Guangzhou 510632, China. YCL0412@163.net
Shen
Bing
B
Ren
Xian-Da
XD
Luo
Rong-Jing
RJ
Ding
Sheng-Yuan
SY
Yan
Fu-Man
FM
Jiang
Jia-Hua
JH
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*
D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D019789:Tetraethylammonium; D000109:Acetylcholine