Effects of docosahexaenoic acid on BK channel open probabilities in coronary smooth muscle cells of diabetic rat

Abstract

Objective To investigate the effects of docosahexaenoic acid (DHA) on large conductance Ca2+- activated K+ channel (BK channel) open probabilities (NP0) in coronary smooth muscle cells of diabetic rats. Methods Streptozotocin-induced diabetic rat animal model was established by injection intraperitoneally. Male SD rats (n=20) with weight of (200±20) g and age of 6-8 weeks were divided into diabetic group (n=10) and normal control group (n=10) by random number table method. Diabetic group was injected intraperitoneally with streptozotocin. Blood glucose was tested after 2 weeks. If it was less than 300 mg/dl, same dose streptozotocin was injected intraperitoneally again. Diabetes was diagnosed until blood glucose was more than 300 mg/dl for 8 weeks. The control group was injected by normal saline. Coronary smooth muscle cells in control and diabetic rats were isolated immediately by enzyme digestion method. The BK currents in coronary smooth muscle cells of control and diabetic group were recorded by single channel patch-clamp technique. Effects of DHA on NP0 of BK channels in coronary smooth muscle cells of control and diabetic rats were compared. Studentt test or Wilcoxon rank test were used to compare the NP0 between control and diabetic groups. One-way ANOVA or M test were applied to compare the NP0 in different DHA concentrations groups. Results When test potentials were at 0, 20, 40, 60, 80, 100, 120 mV, NP0 of BK channels increased with test potentials in both control and diabetic group (F=15.28, 9.72, allP 0.05). At 3, 5 and 10 μmol/L, DHA activated BK channels in a dose- dependent manner in both control group and diabetic group (F=10.21 ,7.32, allP<0.05). The NP0 were lower in diabetic group than in control group at the same DHA concentrations (t=2.71 - 8.54, allP<0.05). Conclusion BK tunnel capacity of the coronary smooth muscle cells in diabetic rats was impared. The protective effects of DHA on diabetic heart may be performed by activating BK channels, increasing NP0 and dilating coronary arteries. Key words: Docosahexaenoic acid; Diabetes mellitus; Coronary artery; Large conductance Ca2+-activated K+ channel; Patch-clamp