Effects of 11,12- Epoxyeicosatrienoic Acids on Calcium-Activated Potassium Channel of Airway Smooth Muscle Cells in COPD Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

XIAO Xinrong , PENG Huasheng , XU Xianhua , HU Meng , YAN Xiang , ZHANG Ru ,  SUN Meiqin.

The Senior Cadre Ward, General Hospital of Chengdu Military Command.Chengdu, Sichuan, 610083, China;

Corresponding author：

SUN Meiqin., Email: xiaoxinrong1963@yahoo.com.cn

Keywords：

Chronic obstructive pulmonary disease; Airway smooth muscle cells; Ca2 + activated K+ channels; Epoxyeicosatrienoic acid

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Objective To explore the activity of Ca2 + -activated K+ ( KCa) inairwaysmoothmuscle cells( ASMCs) in a rat model of chronic obstructive pulmonary disease( COPD) , and to observe the effect of 11, 12-Epoxyeicosatrienoic acid( 11, 12-EETs) on the KCa channel of ASMCs. Methods Forty male Sprague-Dawley rats were randomly assigned to a COPD group and a normal control group. The rats in the COPD group were exposed to cigarette smoking in a relatively closed chamber to induce COPD. The ASMCs were isolated from small bronchi using an acute enzymatic digestion method. In the symmetrical high K+ solution,the KCa currents were separated with inside-out configuration using the patch clamp technique. The activity of KCa currents in ASMCs between the COPD group and the normal group were compared and the effect of 11, 12-EETs on KCa channel was recorded. The opening probability( Po) , opening time( To) and closing time ( Tc) of the KCa were measured. Results Compared with the normal group, Po of KCa in the COPD rats was much shorter ( 0. 084 ±0. 028 vs 0. 198 ±0. 029, P lt; 0. 01) , To was shorter [ ( 0. 732 ±0. 058) ms vs ( 1. 648 ±0. 152) ms, P lt; 0. 01] and Tc was longer[ ( 12. 259 ±2. 612) ms vs ( 6. 753 ±1. 237) ms, P lt;0. 01] . 11, 12-EETs can evoke the activity of KCa currents of ASMCs in the COPD rats while Po was increased( 0. 227 ±0. 059 vs 0. 084 ±0. 028, P lt; 0. 01) , To was much longer[ ( 2. 068 ±0. 064) ms vs ( 0. 732 ±0. 058) ms, P lt; 0. 01] , and Tc was shorter [ ( 4. 273 ±0. 978) ms vs ( 12. 259 ±2. 612) ms, P lt;0. 01] .Conclusions The results suggest that the decreasing of KCa activity plays an important role in the development of COPD. 11,12-EETs can directly evoke the activity of KCa channel in COPD rats, thus relax the airway smooth muscles.

Citation： XIAO Xinrong,PENG Huasheng,XU Xianhua,HU Meng,YAN Xiang,ZHANG Ru,SUN Meiqin.. Effects of 11,12- Epoxyeicosatrienoic Acids on Calcium-Activated Potassium Channel of Airway Smooth Muscle Cells in COPD Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(2): 122-126. doi: Copy

1.	Marc D, Dany S, Sophie B, et al. Epoxyeicosatrienoic acids relax airway smooth muscles and directly activate reconstituted KCa channels. AmJ Physiol Lung Cell Mol Physiol, 1998, 275: 423-431.
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3.	肖欣荣, 陈文彬, 程德云, 等. 脱氢表雄甾酮对缺氧慢性大鼠肺动脉平滑肌细胞钙激活性钾通道的作用. 中华结核和呼吸杂志, 2004, 27: 41-45.
4.	Peng W, Hoidal JR, Karwande SV, et al. Effect of chronic hypoxia on K + channels: regulation in human pulmonary vascular smooth muscle cells. Am J Physiol, 1997, 272: C1271-C1278.
5.	Wellman GC, Bonev AD, Nelson MT, et al. Gender differences in coronary artery diameter involve estrogen, nitric oxide and Ca2 +dependent K + channels. Circ Res, 1996, 79: 1024-1030.
6.	Bonnet S, Savineau JP, Barillot W, et al. Role of Ca( 2 + ) -sensitive K( + ) channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases. Cardiovas Res, 2003, 60 :326-336.
7.	Capdevila J, Chacos N, Werringloer J, et al. Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid. Proc Natl Acad Sci USA, 1981, 78: 5362-5366.
8.	Fisslthaler B, Popp R, Kiss L, et al. Cytochrume P-450 2C is an EDHF synthase in coronary arteries. Nature, 1999, 401: 493-497.
9.	Knot HJ, Standen NB, Nelson MT. Ryanodine receptors regulate arterial diameter and wall [ Ca2 + ] in cerebral arteries of rat via Ca2+ -dependent K+ channels. J Physiol, 1998, 508: 211-221.
10.	Brayden JE, Nelson MT. Regulation of arterial tone by activation of calcium-dependent potassium channels. Science, 1992 , 256 : 532 -535.

1. Marc D, Dany S, Sophie B, et al. Epoxyeicosatrienoic acids relax airway smooth muscles and directly activate reconstituted KCa channels. AmJ Physiol Lung Cell Mol Physiol, 1998, 275: 423-431.
2. 王慧, 程德云, 关键, 等. 单核细胞趋化蛋白-1 与COPD 大鼠气道炎症的研究. 四川大学学报( 医学版) , 2004, 35: 634-637.
3. 肖欣荣, 陈文彬, 程德云, 等. 脱氢表雄甾酮对缺氧慢性大鼠肺动脉平滑肌细胞钙激活性钾通道的作用. 中华结核和呼吸杂志, 2004, 27: 41-45.
4. Peng W, Hoidal JR, Karwande SV, et al. Effect of chronic hypoxia on K + channels: regulation in human pulmonary vascular smooth muscle cells. Am J Physiol, 1997, 272: C1271-C1278.
5. Wellman GC, Bonev AD, Nelson MT, et al. Gender differences in coronary artery diameter involve estrogen, nitric oxide and Ca2 +dependent K + channels. Circ Res, 1996, 79: 1024-1030.
6. Bonnet S, Savineau JP, Barillot W, et al. Role of Ca( 2 + ) -sensitive K( + ) channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases. Cardiovas Res, 2003, 60 :326-336.
7. Capdevila J, Chacos N, Werringloer J, et al. Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid. Proc Natl Acad Sci USA, 1981, 78: 5362-5366.
8. Fisslthaler B, Popp R, Kiss L, et al. Cytochrume P-450 2C is an EDHF synthase in coronary arteries. Nature, 1999, 401: 493-497.
9. Knot HJ, Standen NB, Nelson MT. Ryanodine receptors regulate arterial diameter and wall [ Ca2 + ] in cerebral arteries of rat via Ca2+ -dependent K+ channels. J Physiol, 1998, 508: 211-221.
10. Brayden JE, Nelson MT. Regulation of arterial tone by activation of calcium-dependent potassium channels. Science, 1992 , 256 : 532 -535.

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