Regulation of a hyperpolarization‐activated chloride current in murine respiratory ciliated cells

Regulation of a hyperpolarization‐activated chloride current in murine respiratory ciliated cells
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小鼠呼吸道纤毛细胞超极化激活氯电流的调节

DOI:
10.1111/j.1469-7793.2000.00353.x
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发表时间:
2000
期刊:
The Journal of Physiology
影响因子:
--
通讯作者:
M. Gray
M. Gray
中科院分区:
--
文献类型:
--
作者:
R. Tarran;B. Argent;M. Gray

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1用全细胞膜片钳技术研究了小鼠纤毛呼吸细胞超极化激活的ClACT电流(IHyp-−)的特性。2电流-电压关系是向内整流的,这是由于通道的电压依赖门控所致。3内向电流对细胞外Cl-−浓度非常敏感,这种作用与跨膜Cl-−梯度的变化无关。当细胞外氯−浓度降至6 mM时,内向电流降低70%,其剂量-反应关系的希尔系数为≈2.0,IC_(50)为29 mM。4外阴离子取代得到的选择性顺序为:BR−>I−>Cl−>葡萄糖酸=天冬氨酸。卤化物越多,电流密度越大,而阴离子越少,电流密度越低,表明细胞外阴离子对通道活动是重要的。5细胞内钙离子浓度从0·1增加到0·5μM时,电流密度随细胞内钙浓度的增加而降低,提示Ihyp-ACT不参与容量调节或cAMP/Ca~(2+)刺激的液体分泌。6细胞外pH降至5.0不可逆地抑制Ihyp-ACT。然而,该电流在pH为5·4-9·0的范围内是完全激活的,因此在生理条件下不太可能受到胞外pH的调节。7我们推测Ihyp-ACT可能在基础氯−吸收中起作用,作为一种氯−感受器来维持最佳的呼吸道表面液体的体积和组成。
1 The properties of a hyperpolarization‐activated Cl− current (Ihyp‐act) in murine ciliated respiratory cells have been studied using whole cell patch clamping. 2 The current‐voltage relationship was inwardly rectifying which was due to voltage‐dependent gating of the channel. 3 Inward current was markedly sensitive to the extracellular Cl− concentration, an effect that was not related to changes in transmembrane Cl− gradient. Decreasing extracellular Cl− concentration to 6 mM caused a 70 % reduction in inward current with the dose‐response relationship exhibiting a Hill coefficient of ≈2·0 and an IC50 of 29 mM. 4 External anion replacement gave a selectivity sequence of Br− > I− > Cl− > gluconate = aspartate. The more permeant halides significantly increased current density while the less permeant anions decreased current density, indicating that an extracellular anion is important for channel activity. 5 The conductance was unaffected by exposure to anisotonic pipette solutions or to increases in intracellular cAMP; however, current density was reduced dose dependently by increases in intracellular calcium concentration from 0·1 to 0·5 μM. These results indicate that Ihyp‐act is unlikely to be involved in either volume regulation or cAMP/Ca2+‐stimulated fluid secretion. 6 Decreasing extracellular pH to 5·0 irreversibly inhibited Ihyp‐act. However, the current was fully active over the pH range 5·4‐9·0 making it unlikely that it is modulated by extracellular pH under physiological conditions. 7 We speculate that Ihyp‐act may have a role in basal Cl− absorption, acting as a Cl− sensor to maintain optimal volume and composition of airway surface liquid.
CFTR 氯离子通道的丧失会改变体外囊性纤维化气道上皮对盐的吸收。
DOI: 10.1016/s1097-2765(00)80284-1
发表时间: 1998
期刊: Molecular cell
影响因子: 16
作者:
Zabner,J;Smith,JJ;Karp,PH;Widdicombe,JH;Welsh,MJ
通讯作者: Welsh,MJ
DOI: 10.1152/ajpcell.1995.268.1.c191
发表时间: 1995
期刊: The American journal of physiology
影响因子: --
作者:
D. Malinowska;E. Kupert;A. Bahinski;A. M. Sherry;J. Cuppoletti
通讯作者: D. Malinowska;E. Kupert;A. Bahinski;A. M. Sherry;J. Cuppoletti