Plasma membrane depolarization and disturbed Na+ homeostasis induced by the protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon in isolated nerve terminals.
Plasma membrane depolarization and disturbed Na+ homeostasis induced by the protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon in isolated nerve terminals.
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离体神经末梢中质子载体羰基氰-对三氟甲氧基苯-腙引起的质膜去极化和钠稳态紊乱。
作者：
L. Tretter;C. Chinopoulos;V. Ádám‐Vizi
研究了原基团羰基氰化物-对三氟甲氧基苯基腙（FCCP）对离体神经末段胞内[Na+]、pH和质膜电位的影响。FCCP诱导[Na+]i的升高，甚至低于通常在完整细胞中用于消除线粒体对Ca2+摄取的浓度（0.025-1微米）。fccp诱导的[Na+]i的升高与ATP水平和ATP/ADP比值的下降相关。此外，加入FCCP（1微米）后，细胞内质子浓度（[H+]i）从83 +/- 0.4突然上升到124 +/- 0.7 nM。在[H+]i升高的同时，检测到一个突然的去极化，随后质膜电位缓慢下降。pHi变化的程度和质膜的快速去极化与跨质膜的质子电化学梯度成正比；当这个梯度增加时，检测到更大的去极化。当介质中不含Na+时，快速去极化后膜电位的缓慢下降被消除。我们得出结论，FCCP(1)通过使质膜电位接近质子平衡电位而引起去极化；(2)由于ATP水平和ATP/ADP比值不足而导致细胞内[Na+]增强，从而为Na+，K+/ATP酶提供燃料。由于在质子载体存在的情况下，受到干扰的Na+稳态和质膜去极化都可能严重干扰Ca2+稳态，因此考虑这些改变可能有助于阐明细胞Ca2+固存过程。
The effect of the protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon (FCCP) was studied on the intracellular [Na+], pH, and plasma membrane potential in isolated nerve terminals. FCCP induced a rise of [Na+]i at, and even below, the concentrations (0.025-1 microM) in which it is usually used in intact cells to eliminate Ca2+ uptake by mitochondria. The FCCP-induced increase of [Na+]i correlates with a fall in both the ATP level and the ATP/ADP ratio. In addition, a sudden rise of the intracellular proton concentration ([H+]i) from 83 +/- 0.4 to 124 +/- 0.7 nM was observed on the addition of FCCP (1 microM). Parallel with the rise in [H+]i, an abrupt depolarization was detected, followed by a slower decrease in the plasma membrane potential. Both the extent of the pHi change and the fast depolarization of the plasma membrane were proportional to the proton electrochemical gradient across the plasma membrane; when this gradient was increased, greater depolarization was detected. The slower decrease of the membrane potential after the fast initial depolarization was abolished when the medium contained no Na+. It is concluded that FCCP (1) gives rise to a depolarization by setting the plasma membrane potential close to the proton equilibrium potential and (2) enhances the intracellular [Na+] as a consequence of an insufficient ATP level and ATP/ADP ratio to fuel the Na+,K+/ATPase. Because both disturbed Na+ homeostasis and plasma membrane depolarization could profoundly interfere with Ca2+ homeostasis in the presence of protonophores, consideration given to these alterations may help to clarify the cellular Ca2+ sequestration processes.
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DOI：
10.1113/jphysiol.1997.sp021839
发表时间：
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期刊：
The Journal of physiology
影响因子：
--
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DOI：
--
发表时间：
1995
期刊：
Molecular pharmacology.
影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Costa,E