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
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
复制标题
DOI：
10.1016/s0022-2828(85)80119-x
复制
发表时间：
1985-01-01
影响因子：
5
通讯作者：
VIGNE, P
中科院分区：
文献类型：
--
作者：
LAZDUNSKI, M;FRELIN, C;VIGNE, P
本文描述了鸡心肌细胞中阿米洛利敏感性Na+/H+逆向转运蛋白的性质，并与其他细胞系统中已知的性质进行了比较，分析了Na+/H+交换蛋白在调节细胞内Na+浓度和pH值中的作用。在已研究的不同性质中，可以提到：（i）外部Na+浓度（[Na+]o）依赖性：活性随[Na+] o的增加而增加（KNa+=20 mm）;（ii）外部pH（pHo）依赖性：交换剂活性随pHo增加而增加（pHmo=7.05和Hill系数=1）;（iii）内部pH（pHi）依赖性：当内部pH（pHi）降低时，交换剂的活性以协同的方式增加（pH_（mi）=7.35，Hill系数=3）;（iv）阿米洛利的衍生物比阿米洛利本身的效力高200倍（Kethylisopropylamiloride=30 nm），对Na ~+/H ~+交换系统有选择性，对Na ~+/Ca ~（2+）交换系统无选择性，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。然后反向转运蛋白作为Na+的摄取系统，使用由其他pH调节机制产生的H+梯度。哇巴因处理心肌细胞抑制Na+外流，并产生细胞内Na+活性的增加。用乙基异丙基氨氯吡咪表明，Na+/H+交换系统是洋地黄作用中Na+进入和蓄积的主要途径。正如预期的那样，发现通过Na+/H+反向转运蛋白阻断Na+进入的阿米洛利衍生物拮抗哇巴因对心脏细胞的作用。当心肌细胞内pH降低时，Na+/H+交换器成为主要的pH调节系统。它是心脏细胞从细胞酸中毒中恢复的基本系统。这种情况是由于交换剂在酸性pH下的活性增加和其他pH调节系统的活性降低。我们提出，在本文中，Na+/H+交换系统中起着关键作用的Na+积累，随后的Ca 2+积累，这是观察到缺血心脏再灌注。
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+]oincreases (KNa+=20 mm); (ii) The external pH (pHo) dependence: the activity of the exchanger increases when pHoincreases (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 pHiregulatory 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 pHiregulating 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 pHiand to a decreased activity of other pHiregulatory 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.