Ionic events during the volume response of human peripheral blood lymphocytes to hypotonic media. II. Volume- and time-dependent activation and inactivation of ion transport pathways.

Ionic events during the volume response of human peripheral blood lymphocytes to hypotonic media. II. Volume- and time-dependent activation and inactivation of ion transport pathways.
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DOI:
10.1085/jgp.83.4.513
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发表时间:
1984-04
影响因子:
3.8
通讯作者:
Rothstein, A
Rothstein, A
中科院分区:
医学2区
文献类型:
--
作者:
Sarkadi, B;Mack, E;Rothstein, A

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低渗稀释的人外周血淋巴细胞(PBL)诱导K+和Cl-的大的传导渗透性,与细胞调节其体积的能力。当通过添加离子载体短杆菌肽确保快速阳离子泄漏时,可以独立地检查阴离子电导途径的行为。使用这种技术,它表明,体积诱导激活的Cl-转运被触发的阈值约为1.15 X等渗细胞体积。如果细胞的体积增加到这个水平或以上,则Cl-转运系统被激活,而如果肿胀细胞的体积降低到阈值以下,则Cl-转运失活。激活和失活是独立的相对体积的变化和实际的细胞Na+,K+,或Cl-浓度,以及PBL中的膜电位的变化。当净盐运动和体积变化被K+转运的特异性阻断剂抑制时(例如,奎宁,或Ca 2+耗竭),体积诱导的Cl-电导显示出时间依赖性失活,具有5-8 min的半衰期。Cl-电导,当激活时,似乎涉及全或无响应。与此相反,体积诱导的K+电导是一个分级的反应,与K+通量的增加大致成正比的低渗诱导的细胞体积的增加。数据表明,在淋巴细胞的体积反应在低渗介质中,阴离子电导增加的数量级,超过K+电导,使体积减少(KCl流出)的速率是由一个分级的改变K+电导。当细胞体积接近等渗值时,它通过阴离子电导途径的失活而稳定。
Hypotonic dilution of human peripheral blood lymphocytes (PBL) induces large conductive permeabilities for K+ and Cl-, associated with the capacity of the cells to regulate their volumes. When rapid cation leakage is assured by the addition of the ionophore gramicidin, the behavior of the anion conductance pathway can be independently examined. Using this technique it is demonstrated that the volume- induced activation of Cl- transport is triggered at a threshold of approximately 1.15 X isotonic cell volume. If the volume of a cell is increased to this level or above, the Cl- transport system is activated, whereas if the volume of a swollen cell is decreased below the threshold value, the Cl- transport is inactivated. Activation and inactivation are independent of the relative volume changes and of the actual cellular Na+, K+, or Cl- concentrations, as well as of the changes in membrane potential in PBL. When net salt movement and thus volume change are inhibited by specific blockers of K+ transport (e.g., quinine, or Ca2+ depletion), volume-induced Cl- conductance shows a time-dependent inactivation, with a half-time of 5-8 min. The Cl- conductance, when activated, appears to involve an all-or-none response. In contrast, volume-induced K+ conductance is a graded response, with the increase in K+ flux being roughly proportional to the hypotonicity-induced increase in cell volume. The data indicate that during lymphocyte volume response in hypotonic media, anion conductance increases by orders of magnitude, exceeding the K+ conductance, so that the rate of the volume decrease (KCl efflux) is determined by a graded alteration in K+ conductance. When the cell volume approaches the isotonic value, it is stabilized by the inactivation of the anion conductance pathway.