Ionic events during the volume response of human peripheral blood lymphocytes to hypotonic media. I. Distinctions between volume-activated Cl- and K+ conductance pathways.

Ionic events during the volume response of human peripheral blood lymphocytes to hypotonic media. I. Distinctions between volume-activated Cl- and K+ conductance pathways.
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DOI:
10.1085/jgp.83.4.497
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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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人外周血淋巴细胞(PBL)被置于低渗介质中时,由于KCl通过体积激活的K+和阴离子渗透途径迅速渗漏,首先膨胀,然后收缩到其原始体积。通过使用形成阳离子通道的阳离子载体ghicidin,可以分流通过细胞膜的阳离子运输,从而使盐通量和体积变化受到阴离子净移动速度的限制。“革兰西丁法”辅以体积诱导离子通量的直接测量,可用于评估药物和各种治疗方法对阳离子和阴离子渗透性的影响。结果表明,奎宁和西替地尔是容量诱导的K+转运的阻断剂,而潘生丁、DIDS和Nip-牛磺酸仅抑制容量诱导的Cl-转运。寡霉素同时阻断阳离子和阴离子转运途径,其中寡霉素A更有效地抑制K+转运,而寡霉素C优先阻断氯离子转运。外周血淋巴细胞中钙离子的耗竭可取消容量诱导的K+转运,但对氯离子转运无影响。离子载体A23187恢复细胞内钙离子后,可立即恢复钾离子的快速转运,而不会显著影响容量诱导的氯离子转运。这些观察与其他已报道的信息结合在一起,可以用一个模型最好地解释,在该模型中,细胞膨胀激活了独立的Cl-和K+电导通路,后者在性质上类似于在各种细胞膜上观察到的钙激活的K+转运。
Human peripheral blood lymphocytes (PBL), when placed into hypotonic media, first swell and then shrink back to their original volumes because of a rapid KCl leakage via volume-activated K+ and anion permeation pathways. By using gramicidin, a cation channel-forming ionophore, cation transport through the cell membrane can be shunted so that the salt fluxes and thus the volume changes are limited by the rate of the net anion movements. The "gramicidin method," supplemented with direct measurements of volume-induced ion fluxes, can be used to assess the effects of drugs and of various treatments on cation and anion permeabilities. It is demonstrated that quinine and cetiedil are much more effective blockers of volume-induced K+ transport than of Cl- transport, while dipyridamole, DIDS, and NIP-taurine inhibit only volume-induced Cl- movement. Oligomycins block both cation and anion transport pathways, oligomycin A being more effective in inhibiting K+ transport and oligomycin C preferentially blocking Cl- movement. Ca depletion of PBL abolishes volume-induced K+ transport but has no effect on Cl- transport. Repletion of cell calcium by ionophore A23187 immediately restores rapid K+ transport without significantly affecting volume-induced Cl- transport. These observations, taken together with other reported information, can be best explained by a model in which cell swelling activates independent Cl- and K+ conductance pathways, the latter being similar in properties to the Ca2+-activated K+ transport observed in various cell membranes.