A swelling-activated chloride current in rat sympathetic neurones

A swelling-activated chloride current in rat sympathetic neurones
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DOI:
10.1111/j.1469-7793.1997.555bm.x
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发表时间:
1997-06-15
影响因子:
5.5
通讯作者:
Brown, DA
Brown, DA
中科院分区:
医学1区
文献类型:
--
作者:
Leaney, JL;Marsh, SJ;Brown, DA

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1.我们已经测试了神经元是否表现出肿胀诱导的Cl-电流后低渗休克,通过记录膜电流反应和细胞体积的变化,在电压钳离体大鼠交感神经元在应用低渗溶液。使用全细胞和穿孔膜片记录方法,低渗溶液引起细胞肿胀和在-60 MV的内向Cl-电流的激活。该电流表现出弱的外向整流,没有明显的时间依赖性。SITS(0.3- 1 mM)、NPPB(30-300 μ M)和尼氟灭酸(50-200 μ M)均能抑制该作用,但三苯氧胺(10 μ M)不抑制该作用.低渗溶液没有引起细胞内钙离子浓度的上升,同时indo-1荧光测定。此外,体积变化和Cl-电流均不受EGTA去除外部Ca 2+或内部Ca 2+缓冲至小于或等于nM的影响。Cl-电流不受蛋白激酶C(PKC; GF 109203 X,3 μ M)抑制剂或从移液器溶液中省略ATP的影响。在持续暴露于低渗溶液期间,细胞表现出调节性体积减少。这是完全抑制0.5 mM尼氟灭酸。6.可以得出结论,渗透性肿胀诱导外向整流,Ca 2+和PKC-独立的Cl-电流在这些神经细胞。有人建议,这种电流可能参与音量调节机制。
1. We have tested whether neurones show a swelling-induced Cl- current following hypotonic shock, by recording membrane current responses and cell volume changes in voltage clamped isolated rat sympathetic neurones during application of hypotonic solutions.2. Using both whole-cell and perforated patch recording methods, hypotonic solution caused cell swelling and the activation of an inward Cl- current at -6O MV. This current showed weak outward rectification with no obvious time dependence. It was inhibited by SITS (0.3-1mM), NPPB (30-300 mu M) and niflumic acid (50-200 mu M), but not by tamoxifen (10 mu M).3. Hypotonic solution did not cause a rise in intracellular Ca2+ concentration as measured by simultaneous indo-1 fluorescence. Also, neither the volume change nor Cl- current were affected by the removal of external Ca2+ or internal Ca2+ buffering to less than or equal to nM with EGTA.4. The Cl- current was unaffected by an inhibitor of protein kinase C (PKC; GF109203X, 3 mu M) or by omission of ATP from the pipette solution.5. Cells exhibited a regulatory volume decrease during sustained exposure to hypotonic solution. This was completely inhibited by 0.5 mM niflumic acid.6. It is concluded that osmotic swelling induces an outwardly rectifying, Ca2+- and PKC-independent Cl- current in these nerve cells. It is suggested that this current may be involved in volume regulatory mechanisms.