Ebner F, Korth M, Kühlkamp V
J Physiol. 1986 Oct;379:187-203. doi: 10.1113/jphysiol.1986.sp016247.
[3H]ouabain binding (1.85-500 nmol/l) was evaluated in resting guinea-pig papillary muscles at 1.2-12 mmol K/l. The time course of binding was biphasic. This finding excluded a homogeneous population of non-interacting binding sites of ouabain, even though the identical susceptibility of both phases to K suggested the occupation of similarly operative receptors. Concomitant with ouabain binding, intracellular Na ion activity (aiNa) increased in the presence of 2.4 or 12 mmol K/l. Occupation of the receptor molecule by ouabain, therefore, conformed to Na-pump inhibition. Although K antagonized both ouabain binding and its effect on aiNa, the antagonistic effect on aiNa was more pronounced. The reduction of passive Na influx with depolarization as well as the stimulation of the Na pump by K presumably contributed to the antagonistic effect of K. The decrease in aiNa from 8 to 5 mmol/l, when in the absence of ouabain K was raised from 2.4 to 12.0 mmol/l, confirmed the relevance of Na fluxes. Simultaneous changes in aiNa and in the force of rested-state contractions were apparent upon addition of ouabain. At 2.4 mmol K/l, increase in aiNa raised the force of contraction by constant proportions. At 12 mmol K/l, the inotropic effect produced at comparable values of aiNa was approximately tenfold higher and was susceptible to a change in extracellular Ca concentration. Increase in aiNa, however, was differently effective on force of contraction of low as compared with high values of aiNa. The influence of resting membrane potential on electrogenic Na-Ca exchange is supposed to interfere with the inotropic effectiveness of aiNa after the cell membrane depolarized from -102 mV to -65 mV with the increase of K from 2.4 to 12 mmol/l. In view of the role of both membrane potential and aiNa not just a single mechanism appeared to be involved in the control of force of contraction.
在1.2 - 12 mmol K/l的条件下，对静息豚鼠乳头肌中[3H]哇巴因结合（1.85 - 500 nmol/l）进行了评估。结合的时间进程是双相的。这一发现排除了哇巴因非相互作用结合位点的同质群体，尽管两个阶段对K的相同敏感性表明占据了类似作用的受体。与哇巴因结合同时，在2.4或12 mmol K/l存在时，细胞内Na离子活性（aiNa）增加。因此，哇巴因对受体分子的占据符合钠泵抑制。虽然K拮抗哇巴因结合及其对aiNa的影响，但对aiNa的拮抗作用更明显。随着去极化被动Na内流的减少以及K对钠泵的刺激可能促成了K的拮抗作用。当在无哇巴因的情况下K从2.4 mmol/l升高到12.0 mmol/l时，aiNa从8 mmol/l降至5 mmol/l，证实了Na通量的相关性。加入哇巴因后，aiNa和静息状态收缩力同时发生变化。在2.4 mmol K/l时，aiNa的增加使收缩力按恒定比例增加。在12 mmol K/l时，在可比的aiNa值下产生的变力作用大约高十倍，并且易受细胞外Ca浓度变化的影响。然而，aiNa的增加对低aiNa值与高aiNa值时的收缩力影响不同。随着K从2.4 mmol/l增加到12 mmol/l，细胞膜从 - 102 mV去极化到 - 65 mV，静息膜电位对电致Na - Ca交换的影响被认为会干扰aiNa的变力作用效果。鉴于膜电位和aiNa的作用，似乎不仅仅是单一机制参与收缩力的控制。
