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细胞外La^(3+)对内向整流钾通道(IRK1)的阻断作用 被引量:1

The Blocking Effects of Extracellular La^(3+) on the Inward Rectifier Potassium Channel (IRK1)
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摘要 本文采用双微电极电压钳 (TEV)法研究细胞外La3+对非洲爪蟾卵母细胞表达的内向整流钾通道(IRK1)的阻断作用。细胞外La3+浓度分别为 0 ,0 1,0 3,1,3和 10mmol/L ,K+浓度为 90mmol/L ,可见La3+对IRK1的瞬间电流 (施加电压后 1 5ms)具有La3+浓度依赖性、时间依赖性和电压依赖性阻断作用 ;阻断剂La3+对IRK1的门控特性和外向电流几乎无影响作用 ;细胞外加La3+后反转电位没有变化 ,因而IRK1对之不通透。细胞外La3+在减少IRK1电导的同时增加IRK1的归一化电导。三级指数拟合的结果表明 :拟合的时间常数不随La3+浓度的增减而增减 ,这表明细胞外La3+对IRK1的抑制作用可能通过了表面电荷机制或La3+在通道中的阻断位点在通道表面。因为La3+浓度较低时 ,阻断的效力与La3+浓度较高时的差异不大 ,所以La3+不会通过表面电荷机制进行IRK1阻断的 ,因此La3+是IRK1的一种快速开通道阻断剂 。 Two-microelectrode voltage clamp (TEV) method was used to study the blocking effects of extracellular La 3+ on the inward rectifier potassium channel (IRK1) expressed in the Xenopus oocytes.La 3+ can concentration-,time- and voltage dependently block IRK1 instantaneous currents (1.5 ms after voltage applied) when external La 3+ concentration is 0,0.1,0.3,1,3 or 10 mmol/L with K + concentration fixed to 90mmol/L.La 3+ almost has no effect on the gating property and outward currents of IRK1.La 3+ can concentration-dependently increase the normalized chord conductance of IRK1.IRK1 can not permeate La 3+ because reverse potential did not changed.Three exponential fitting analyze indicates that time constant is not changed with the change of La 3+ concentration.This shows that the inhibitory effects of La 3+ may caused by surface potential or the blocking site of La 3+ is at the surface of the channel.Because External La 3+ can not inhibit IRK1 macroscopic currents more powerful when external La 3+ concentration is lower.These mean that external La 3+ does not work through surface potential mechanism.So Ba 2+ is considered as one fast open channel blocker of IRK1 and its blocking site of La 3+ is at the surface of the channel.
出处 《心肺血管病杂志》 CAS 2000年第4期280-283,共4页 Journal of Cardiovascular and Pulmonary Diseases
基金 国家自然科学基金!(No.39840 0 2 2 ) 全军"九五"医学科研规划第二批留学回国人员科研起动基金!(No.98H0 2 3)
关键词 细胞外La^3+ 内向整流钾通道 电压钳 Lanthanum Open channel blocker Inward rectifier potassium channel
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参考文献5

  • 1Kubo Y,Timothy J,Jan YN,et al.Primary structure and functional expression of a mouse inward rectifier potassium channel[].Nature.1993
  • 2Mackinnon R.Latorre R, Miller C.Role of surface electrostatics in the operation of a high conductance Ca2+ activated K+ channel[].Biochemistry.1989
  • 3Oiki S,Yamamoto T,Okada Y.Apparent stability constants and purity of Cachelating agents evaluated using Ca- selective electrodes by the doublelog optimization method[].Cell Calcium.1994
  • 4Doyle DA,Cabra JM,Richard A,et al.The structure of the potassium channel: molecular Basis of K+ conduction and selectivity[].Science.1998
  • 5Ravshan ZS,Tominaga T,Miwa A,et al.A conserved arginine residue in the preregion of an inward rectifier K channel ( IRK1 ) as an external barrier for cationic blockers[].The Journal of General Physiology.1997

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