Lazdunski M, Kazazoglou T, Renaud J F, Rossi B
Basic Res Cardiol. 1984;79 Suppl:110-8. doi: 10.1007/978-3-642-72376-6_15.
Affinity labelling of the digitalis receptor has indicated that it is situated on the N-terminal part of the alpha-subunit of the (Na+,K+)ATPase. Biochemical and pharmacological properties of the (Na+,K+)ATPase studied on intact chick embryonic hearts and under heart cell culture conditions have indicated the existence of two families of ouabain binding sites i.e.: a low affinity binding sites with a dissociation constant (Kd) of 2-6 microM for the ouabain-receptor complex and a high affinity binding site with a Kd of 26-48 nM. High and low affinity sites also are present at all embryonic stages studied. Inhibition of 86Rb+ uptake in cultured cardiac cells and increase in intracellular Na+ concentration, due to (Na+,K+)ATPase blockade, occur in an ouabain concentration range corresponding to the saturation of the low affinity ouabain site. Ouabain stimulated 45Ca2+ uptake increases in parallel with the increase in the intracellular Na+ concentration. It is suppressed in Na+ free medium or when Na+ is replaced by Li+ suggesting that the increase is due to the indirect activation of the Na+/Ca2+ exchange system in the plasma membrane. Dose-response curves for the inotropic effects of ouabain on papillary muscle and on ventricular cells in culture indicate the development of the cardiotonic properties is parallel to the saturation of the low affinity binding site for ouabain. Therefore, inhibition of the cardiac (Na+,K+)ATPase corresponding to low affinity ouabain binding sites seems to be responsible for both the cardiotonic and cardiotoxic effects of the drug.
洋地黄受体的亲和标记表明它位于（Na⁺，K⁺）ATP酶α亚基的N端部分。在完整的鸡胚心脏以及心脏细胞培养条件下对（Na⁺，K⁺）ATP酶的生化和药理学特性研究表明存在两类哇巴因结合位点，即：一类是低亲和力结合位点，哇巴因 - 受体复合物的解离常数（Kd）为2 - 6微摩尔，另一类是高亲和力结合位点，Kd为26 - 48纳摩尔。在所研究的所有胚胎阶段也都存在高亲和力和低亲和力位点。由于（Na⁺，K⁺）ATP酶被阻断，培养的心脏细胞中⁸⁶Rb⁺摄取的抑制以及细胞内Na⁺浓度的增加，发生在与低亲和力哇巴因位点饱和相对应的哇巴因浓度范围内。哇巴因刺激的⁴⁵Ca²⁺摄取增加与细胞内Na⁺浓度的增加平行。在无Na⁺培养基中或当Na⁺被Li⁺替代时，这种增加受到抑制，这表明该增加是由于质膜中Na⁺/Ca²⁺交换系统的间接激活。哇巴因对乳头肌和培养的心室细胞的变力作用的剂量 - 反应曲线表明强心特性的发展与哇巴因低亲和力结合位点的饱和平行。因此，与低亲和力哇巴因结合位点相对应的心脏（Na⁺，K⁺）ATP酶的抑制似乎是该药物强心和心脏毒性作用的原因。
