心脏细胞中的钠/氢交换系统：其生化和药理学特性及其在调节细胞内钠浓度和细胞内pH值方面的作用。
The sodium/hydrogen exchange system in cardiac cells: its biochemical and pharmacological properties and its role in regulating internal concentrations of sodium and internal pH.
作者信息
Lazdunski M, Frelin C, Vigne P
出版信息
J Mol Cell Cardiol. 1985 Nov;17(11):1029-42. doi: 10.1016/s0022-2828(85)80119-x.
This paper describes the properties of the amiloride-sensitive Na+/H+ antiporter in chick cardiac cells, compares them with those known in other cellular systems and analyzes the role of the Na+/H+ exchanger in the regulation of internal Na+ concentrations and internal pH. Among the different properties which have been studied one can mention: (i) The external Na+ concentration [( Na+]o) dependence: the activity increases when [Na+]o increases (KNa+ = 20 mM); (ii) The external pH (pHo) dependence: the activity of the exchanger increases when pHo increases (pHmo = 7.05 and Hill coefficient = 1); (iii) The internal pH (pHi) dependence; the activity of the exchanger increases in a cooperative way when internal pH (pHi) decreases (pHmi = 7.35 and Hill coefficient = 3); (iv) There are derivatives of amiloride which are 200 times more potent than amiloride itself (Kethylisopropylamiloride = 30 nM) and which are selective on the Na+/H+ exchange system v. other Na+ transporting system including the Na+/Ca2+ exchange system. Under physiological conditions, the Na+/H+ exchange system contributes little to the regulation of the internal pH of chick cardiac cells. The antiporter then serves as an uptake system for Na+ using the H+ gradient created by other pHi regulatory mechanisms. Treatment of cardiac cells with ouabain inhibits Na+ efflux and produced an increase in intracellular Na+ activity. Ethylisopropylamiloride was used to show that the Na+/H+ exchange system is the main pathway for Na+ entry and accumulation in digitalis action. As expected amiloride derivatives which block Na+ entry via the Na+/H+ antiporter were found to antagonize ouabain action on cardiac cells. When the internal pH of cardiac cells is lowered, the Na+/H+ exchanger becomes the major pHi regulating system. It is the essential system by which cardiac cells recover from cellular acidosis. The situation is due both to an increased activity of the exchanger at acidic pHi and to a decreased activity of other pHi regulatory systems. We propose in this paper that the Na+/H+ exchange system plays a key role in Na+ accumulation followed by Ca2+ accumulation which is observed when ischemic hearts are reperfused.
本文描述了鸡心肌细胞中对阿米洛利敏感的Na⁺/H⁺逆向转运体的特性，将其与其他细胞系统中已知的特性进行比较，并分析了Na⁺/H⁺交换体在调节细胞内Na⁺浓度和细胞内pH值中的作用。在已研究的不同特性中，可以提及：（i）外部Na⁺浓度[（Na⁺）ₒ]依赖性：当[Na⁺]ₒ增加时活性增加（KNa⁺ = 20 mM）；（ii）外部pH（pHₒ）依赖性：当pHₒ增加时交换体的活性增加（pHmₒ = 7.05且希尔系数 = 1）；（iii）内部pH（pHi）依赖性；当细胞内pH（pHi）降低时，交换体的活性以协同方式增加（pHmᵢ = 7.35且希尔系数 = 3）；（iv）存在比阿米洛利本身效力强200倍的阿米洛利衍生物（乙基异丙基阿米洛利 = 30 nM），并且它们对Na⁺/H⁺交换系统具有选择性，相对于其他包括Na⁺/Ca²⁺交换系统在内 的Na⁺转运系统。在生理条件下，Na⁺/H⁺交换系统对鸡心肌细胞内pH的调节作用很小。然后，该逆向转运体作为利用其他pHi调节机制产生的H⁺梯度摄取Na⁺的系统。用哇巴因处理心肌细胞会抑制Na⁺外流并导致细胞内Na⁺活性增加。乙基异丙基阿米洛利用于表明Na⁺/H⁺交换系统是洋地黄作用中Na⁺进入和积累的主要途径。正如预期的那样，发现通过Na⁺/H⁺逆向转运体阻断Na⁺进入的阿米洛利衍生物可拮抗哇巴因对心肌细胞的作用。当心肌细胞的细胞内pH降低时，Na⁺/H⁺交换体成为主要的pHi调节系统。它是心肌细胞从细胞酸中毒中恢复的关键系统。这种情况既是由于在酸性pHi时交换体活性增加，也是由于其他pHi调节系统活性降低。我们在本文中提出，Na⁺/H⁺交换系统在缺血心脏再灌注时观察到的Na⁺积累随后Ca²⁺积累中起关键作用。
Zotero 插件