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尼氟灭酸通过钙库钙释放引起豚鼠耳蜗螺旋动脉平滑肌细胞超极化

李丽, 马克涛, 赵磊, 司军强

华中科技大学同济医学院药理学系.湖北,武汉 430030；石河子大学地方与民族高发病教育部省部共建重点实验室电生理研究室.新疆,石河子 832002

摘要

该研究旨在观察氯离子通道阻断剂尼氟灭酸(niflumic acid,NFA)引起豚鼠耳蜗螺旋动脉平滑肌细胞产生超极化的机制。以豚鼠为实验动物,运用细胞内微电极和全细胞膜片钳记录技术,观察NFA和其它药物对急性分离的耳蜗螺旋动脉平滑肌细胞的作用。结果显示:NFA、indanyloxyacetic acid94(IAA--94)和disodium4,4'--diisothiocyanatostilbene--2,2'--disulfonate(DIDS)可使低静息膜电位的细胞产生超极化,但对高静息膜电位的细胞无明显作用。低静息膜电位细胞的平均静息电位为(--42.47±1.38)mV({sl n}=24),100#mu#mol/L NFA、10#mu#mol/L IAA--94和200#mu#mol/L DIDS分别使细胞超极化至(13.7±4.3)mV({sl n}=9,{sl P}<0.01),(11.4±4.2)mV({sl n}=7,{sl P}<0.01)和(12.3±3.7)mV({sl n}=8,{sl P}<0.01),这种氯离子通道阻断剂引起细胞超极化反应的效应呈浓度依赖性。NFA引起的超极化和外向电流几乎完全被100nmol/L iberiotoxin、100nmol/L charybdotoxin、10mmol/L tetraethylammonium、50#mu#mol/L BAPTA--AM、10#mu#mol/L ryanodine和0.1---10mmol/L caffeine阻断,但不能被100#mu#mol/L nifedipine、100#mu#mol/L CdCl_(2)和无Ca~(2+)灌流外液阻断。结果提示:氯离子通道的阻断剂NFA可通过平滑肌细胞内钙库的钙释放增加细胞内钙,进而激活钙依赖的钾通道,产生耳蜗螺旋动脉平滑肌细胞的超极化反应。

关键词： 耳蜗螺旋动脉; 平滑肌细胞; 尼氟灭酸; 超极化; 钙库

Niflumic acid hyperpolarizes the smooth muscle cells by opening BK_(Ca) channels through ryanodine--sensitive Ca~(2+) release in spiral modiolar artery

Li Li, Ma Ketao, Zhao Lei, Si Junqiang

Department of Pharmacology,Tongji Medical College,Huazhong University of Science and Technology.Wuhan 430030,Hubei；China

Abstract

The mechanism by which niflumic acid(NFA),a Cl-channel antagonist,hyperpolarizes the smooth muscle cells(SMCs) of cochlear spiral modiolar artery(SMA) was explored.Guinea pigs were used as subjects and perforated patch clamp and intracellular recording technique were used to observe NFA-induced response of SMC in the acutely isolated SMA preparation.The results showed that bath application of NFA,indanyloxyacetic acid 94(IAA-94) and disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate(DIDS) caused hyperpolarization and evoked outward currents in all cells at low resting potential(RP),but had no effects in cells at high RP.In the low RP SMCs,the average RP was about(-42.47±1.38) mV(n=24).Application of NFA(100 #mu#mol/L),IAA-94(10 #mu#mol/L) and DIDS(200 #mu#mol/L) shifted the RP to(13.7±4.3) mV(n=9,P<0.01),(11.4±4.2) mV(n=7,P<0.01) and(12.3±3.7) mV(n=8,P<0.01),respectively.These drug-induced responses were in a concentration-dependent manner.NFA-induced hyperpolarization and outward current were almost blocked by charybdotoxin(100 nmol/L),iberiotoxin(100 nmol/L),tetraethylammonium(10 mmol/L),BAPTA-AM(50 #mu#mol/L),ryanodine(10 #mu#mol/L) and caffeine(0.1-10 mmol/L),respectively,but not by nifedipine(100 #mu#mol/L),CdCl_(2)(100 #mu#mol/L) and Ca~(2+)-free medium.It is concluded that NFA induces a release of intracellular calcium from the Ca~(2+) stores and the released intracellular calcium in turn causes concentration-dependent and reversible hyperpolarization and evokes outward currents in the SMCs of the cochlear SMA via activation of the Ca~(2+)-activated potassium channels.

Key words: spiral modiolar artery;Smooth muscle cell;niflumic acid;hyperpolarization;Ca~(2+) stores

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引用本文：

李丽, 马克涛, 赵磊, 司军强. 尼氟灭酸通过钙库钙释放引起豚鼠耳蜗螺旋动脉平滑肌细胞超极化[J]. 生理学报 2008; 60 (6): 743-750.

Li Li, Ma Ketao, Zhao Lei, Si Junqiang. Niflumic acid hyperpolarizes the smooth muscle cells by opening BK_(Ca) channels through ryanodine--sensitive Ca~(2+) release in spiral modiolar artery. Acta Physiol Sin 2008; 60 (6): 743-750 (in Chinese with English abstract).