期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

铅抑制急性分离的大鼠背根神经节慢失活钾电流 被引量：1

Inhibitory effect of Pb^(2+) on slow-inactivating K^+ current in acutely isolated rat dorsal root ganglion neurons
暂未订购
导出
摘要 目的　慢失活外向K+电流 (ID)对于长时程持续刺激中延迟动作电位的发放 ,调节其发放频率和复极化有重要意义 ,其改变对神经元的兴奋性产生重要影响 ,因此研究铅 (Pb2 +)对神经元细胞ID 的效应 ,并初步探讨其作用机理。方法　应用全细胞膜片钳技术 ,根据动力学和药理学特性分离鉴定大鼠背根神经节 (DRG)ID,观察Pb2 +对ID 的抑制效应。结果　Pb2 +以浓度依赖性方式抑制ID。 0 .1,1.0 ,10 .0和 10 0 .0 μmol·L- 1Pb2 +对 + 6 0mV处ID的抑制率分别为 (6 .9± 0 .6 ) %、(2 9.3± 3.0 ) %、(85 .9± 5 .1) %和 (99.4± 7.0 ) % (n =15 ) ,IC50 为2 .4 μmol·L- 1。ID 的激活具有电压依赖性 ,Pb2 +对ID 的抑制作用也具有电压依赖性 ,最大抑制作用发生在 + 6 0mV处。 10 .0 μmol·L- 1Pb2 +使得ID 电流的稳态激活曲线向去极化方向移动 ,并延长ID 的激活时间常数 ,提示Pb2 +增加了ID 的激活时程。结论　Pb2 +显著抑制DRG神经元ID 电流 ,导致神经元的兴奋性增加 ,这可能是Pb2 +影响神经细胞功能的作用机理之一。 AIM Slow inactivating K + current (I D) possesses an important role in delaying the discharge of action potential after a period of long duration, modulating the frequency of the repetitive firing and repolarization. Modulation of I D generates a powerful effect on neuronal excitabi lity. Therefore, the inhibitory effects and mechanism of Pb 2+ on I D were investigated in rat dorsal root ganglion (DRG) neurons. METHODS With the whole cell patch clamp technique, I D was isolated based on the kinetics and pharmacological properties, and the inhibitory effects of Pb 2+ on I D were investigated in rat acutely isolated DRG neurons. RESULTS The results showed that 0.1, 1.0, 10.0 and 100.0 μmol·L -1 Pb 2+ inhibited the amplitude of I D by (6.9±0.6)%, (29.3±3.0)%,(85.9± 5.1)% and (99.4±7.0)%(n=15), respectively, IC 50 was 2.4 μmol·L -1 . It suggested that the inhibition of Pb 2+ on I D be dose dependent and saturated. The activation of I D was voltage dependent, and the inhibition of Pb 2+ was also voltage dependent. The strongest inhibition of Pb 2+ was at +60 mV. The activation curve of I D was shifted to depolarization direction with Pb 2+ . The activation time constant was enlarged with Pb 2+ , suggesting that Pb 2+ increase the activation course of I D. CONCLUSION The inhibition of Pb 2+ on I D significantly increase the excitation of DRG neurons, which maybe take an important part in Pb 2+ neurotoxication.
作者 戴晓青 阮迪云
机构地区 中国科技大学生命科学学院神经毒理学实验室
出处 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2002年第3期176-181,共6页 Chinese Journal of Pharmacology and Toxicology
基金 中国科学院创新项目 (KZCX2 4 10 ) 国家自然科学基金 (30 170 80 9) 国家自然科学基金 (30 0 0 0 0 39) 教育部博士点研究基金(RFDP 19990 35 811) 中国科技大学研究基金 (ky 15 0 4 )~~
关键词 铅 急性分离 大鼠 背根神经节 钾电流 lead rats ganglia, spinal potassium channels patch clamp technique, whole cell
分类号 R994.3 [医药卫生—毒理学]
  • 相关文献

参考文献16

  • 1[1]Dai XQ,Ruan DY,Chen JT.The effects of lead on transient outwards potassium channels in acutely isolated dorsal root ganglion neurons[J].Brain Res,2001,904(3):327-340.
  • 2[2]Ruan DY,Chen JT,Zhao C,Xu YZ,Wang M,Zhao WF.Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyrus following developmental lead exposure in vivo[J].Brain Res,1998,806(2):196-201.
  • 3[3]Büsselberg D,Platt B,Michael D,Carpenter DO,Haas HL.Mammalian voltage-activated calcium channel currents are blocked by Pb2+,Zn2+,and Al3+[J].J Neurophysiol,1994,71(4):1491-1497.
  • 4[4]Madeja M,Mubhoff U,Binding N,Witting U,Speckmann EJ.Effects of Pb2+ on delayed-rectifier potassium channels in acutely isolated hippocampal neurons[J].J Neurophysiol,1997,78(5):2649-2654.
  • 5[5]Storm JF.Temporal integration by a slowly inactivating K+ current in hippocampal neurons[J].Nature,1988,336(6197):379-381.
  • 6[6]Chabbert C,Chambard JM,Sans A,Desmadryl G.Three types of depolarization-activated potassium currents in acutely isolated mouse vestibular neurons[J].J Neurophysiol,2001,85(3):1017-1026.
  • 7[7]Penner R,Petersen M,Pierau F,Dreyer F.Dendrotoxin: a selective blocker of non-inactivating potassium current in guinea-pig dorsal root ganglion neurons[J].Pflügers Arch,1986,407(4):365-369.
  • 8[8]Stansfeld C,Feltz A.Dendrotoxin-sensitive K+ channels in dorsal root ganglion cells[J].Neurosci Lett,1988,93(1):49-55.
  • 9[9]Everill B,Rizzo MA,Kocsis JD.Morphologically identified cutaneous afferent DRG neurons express three different potassium currents in varying proportions[J].J Neurophysiol,1998,79(4):1814-1824.
  • 10[10]Storm JF.Potassium currents in hippocampal pyramidal cell[J].Prog Brain Res,1990,83:161-187.

同被引文献14

  • 1Winneke G,Collet W,Lilienthal H.The effects of lead in laboratory animals and environmentallyexposed children[J].Toxicology,1988,49(2-3):291-298.
  • 2Waldmann R,Lazdunski MH.H(+)-gated cation channels:neuronal acid sensors in the Na C/DEG family of ion channels[J].Curr Opin Neurobiol,1998,8(3):418-424.
  • 3Jordt SE,Bautista DM,Chuang HH,Mckemy DD,Zygmunt PM,Hogestatt ED,et al.Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1[J].Nature,2004,427(6971):260-265.
  • 4Tai C,Zhu SS,Zhou N.TRPA1:the central molecule for chemical sensing in pain pathway?[J].J Neurosci,2008,28(5):1019-1021.
  • 5Bautista DM,Jordt SE,Nikai T,Tsuruda PR,Read AA,Yamoah EN,et al.TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents[J].Cell,2006,124(6):1269-1282.
  • 6Macpherson LJ,Dubin AE,Evans MJ,Schultz PG,Cravatt BF.Noxious compounds activate TRPA1ion channels through covalent modification of cysteines[J].Nature,2007,445(7127):541-545.
  • 7Mc Namara CR,Mandel-Brehm J,Bautista DM,Siemens J,Deranian KL,Zhao M,et al.TRPA1mediates formalin-induced pain[J].Proc Natl Acad Sci,2007,104(33):13525-13530.
  • 8Zygmunt PM,H?gest?tt ED.TRPA1[J].Handb Exp Pharmacol,2014,222:583-630.
  • 9Yuan Y,Lu YP.The research progress of effects of lead on neuronal ion channels[J].生物学教学,2009,34(9):5-6.
  • 10Jang HO,Kim JS,Kwon WC,Kim JK,Kim DH,Kim WI,et al.The effect of lead on calcium release activated calcium influx in primary cultures of human osteoblast-like cells[J].Arch Pharm Res,2008,31(2):188-194.

引证文献1

中国药理学与毒理学杂志
2002年 第3期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部