Transport and pharmacological properties of nine different human Na,K-ATPase isozymes
Transport and pharmacological properties of nine different human Na,K-ATPase isozymes
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DOI：
10.1074/jbc.275.3.1976
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发表时间：
2000-01-21
影响因子：
4.8
通讯作者：
Geering, K
中科院分区：
文献类型：
--
作者：
Crambert, G;Hasler, U;Geering, K
Na，K-ATPase在细胞离子动态平衡中起重要作用，是人体远端神经的药理受体。在非洲爪哇卵母细胞中表达了9种不同的人Na，K-ATPase同工酶，由3种α和β亚型组成，并对其转运和药理性质进行了分析。根据哇巴因结合和K+激活的泵电流测量，所有人的同工酶都是有功能的，但它们的周转率因铜异构体的不同而不同。另一方面，外部K+激活的变化是由α和β亚型之间的协同作用机制决定的，α2-β2络合物具有最低的表观K+亲和力，α亚型影响内Na+亲和力的顺序是α1>；α2>；α3的顺序是电压依赖。所有人的Na，K-ATPase同工酶对哇巴因具有相似的高亲和力，然而，α2-β同工酶表现出比α1-β和α3-β同工酶更快的哇巴因结合和解离速率常数，最后，K+/哇巴因拮抗作用存在异构体特异性差异，可能保护α1而不是α2或α3免受洋地黄在生理K+水平上的抑制。总之，我们的研究揭示了人类Na，K-ATPase同工酶的几个新的功能特征，有助于更好地了解它们在不同组织中的离子动态平衡以及洋地黄的作用和毒性中的作用。
Na,K-ATPase plays a crucial role in cellular ion homeostasis and is the pharmacological receptor for distalis in man. Nine different human Na,K-ATPase isozymes, composed of 3 alpha and beta isoforms, were expressed in Xenopus oocytes and were analyzed for their transport and pharmacological properties. According to ouabain binding and K+-activated pump current measurements, all human isozymes are functional but differ in their turnover rates depending on the cu isoform, On the other hand, variations in external K+ activation are determined by a cooperative interaction mechanism between alpha and beta isoforms with alpha 2-beta 2 complexes having the lowest apparent K+ affinity, alpha Isoforms influence the apparent internal Na+ affinity in the order alpha 1 > alpha 2 > alpha 3 and the voltage dependence in the order alpha 2 > alpha 1 > alpha 3. All human Na,K-ATPase isozymes have a similar, high affinity for ouabain, However, alpha 2-beta isozymes exhibit more rapid ouabain association as well as dissociation rate constants than alpha 1-beta and alpha 3-beta isozymes, Finally, isoform-specific differences exist in the K+/ouabain antagonism which may protect alpha 1 but not alpha 2 or alpha 3 from digitalis inhibition at physiological K+ levels. In conclusion, our study reveals several new functional characteristics of human Na,K-ATPase isozymes which help to better understand their role in ion homeostasis in different tissues and in digitalis action and toxicity.