Lüllmann H, Peters T, Prillwitz H H, Ziegler A
Basic Res Cardiol. 1984;79 Suppl:93-101. doi: 10.1007/978-3-642-72376-6_13.
Remarkable differences exist between the effects of different cardiac glycosides (native and semi-synthetic) with respect to the affinity and to the magnitude of inotropic responses and their time courses. At glycoside concentrations which lead to identical Na-K-ATPase inhibitions, the inotropic responses vary widely. This finding contradicts the hypothesis that the increase of contractile force is the consequence of an ATPase inhibition and causally related to it. We propose the hypothesis that the inhibition of ATPase and the inotropic stimulation provoked by cardiac glycosides are two parallel events, not causally related but both mediated by the same receptor. The inhibition of the Na-K-ATPase is the consequence of the occupation and thus proportional to the concentration of the glycoside-ATPase complexes. In contrast, the inotropic response is determined by the frequency of glycoside-ATPase-interactions. Glycosides which possess high association and dissociation rate constants will interact with the ATPase with high frequencies and thus will evoke larger inotropic responses at a given ATPase inhibition than glycosides with low turnover rates.
不同的强心苷（天然的和半合成的）在亲和力、变力反应的幅度及其时程方面存在显著差异。在导致相同钠钾ATP酶抑制作用的苷浓度下，变力反应差异很大。这一发现与收缩力增加是ATP酶抑制作用的结果且与之有因果关系的假说相矛盾。我们提出假说：强心苷引起的ATP酶抑制作用和变力刺激是两个平行事件，并非因果相关，但均由同一受体介导。钠钾ATP酶的抑制是占据作用的结果，因此与苷 - ATP酶复合物的浓度成正比。相比之下，变力反应则由苷 - ATP酶相互作用的频率决定。具有高缔合和解离速率常数的苷将以高频率与ATP酶相互作用，因此在给定的ATP酶抑制作用下，比周转率低的苷能引发更大的变力反应。
