SODIUM-CALCIUM DEPENDENCE OF RESTING FORCE IN RAT CARDIAC MUSCLE

在未受刺激的离体大鼠心室肌中，静息增加 外力(DeltaRF)，随着外部钙的增加而发生 浓度([Ca~(2+)]e)可通过降低细胞内 通过从灌流液中去除钠来增加钠的含量 通过添加哇巴因来提高细胞钠含量。我们假设 这证明了膜Na/Ca交换的活性。既然是这样 众所周知，膜交换表现出分级的活性，我们试图 通过演示[Na+]i之间的分级反应来扩展我们的观察 和DeltaRF。外部钾浓度([K+]e)设置为逐渐 降低系列中每个实验的值，以给出分级抑制 从而使[Na+]i逐渐升高。[Ca2+]e当时是 从0 mm增加到2 mm，记录DeltaRF。结果表明， 随着[K+]e的减小(从而增大 [Na+]i.因此，不仅Delta[Ca~(2+)]的Delta Rf依赖于 [NA+]e，但以分级的方式进行。这进一步证明了 Na/Ca交换在控制大鼠DeltaRF中的活性 肌肉。在将这些研究扩展到完整的心脏时，我们假设 在无钙期间后，钠离子梯度的大小 钙再灌流的开始将对随后的细胞钙升高进行分级。我们的 结果表明：(1)无钙时心肌细胞Na+升高 和(2)钙离子末端钠离子梯度的大小。 自由期是细胞内钙获得程度的重要决定因素， 细胞K+丢失和钙离子引起的收缩功能降低 重新引入，统称为“钙” 内心的悖论。

In unstimulated isolated, rat ventricular muscle, the increase in resting force (DeltaRF) which occurs with an increase in external calcium concentration (Delta[Ca2+]e can be largely abolished by lowering cellular sodium content by removing sodium from the perfusate and can be potentiated by raising cellular sodium content by adding ouabain. We hypothesized that this demonstrated the activity of a membrane Na/Ca exchange. Since this membrane exchange is well known to exhibit graded activity, we sought to extend our observations by demonstrating a graded response between [Na+]i and DeltaRF. External potassium concentration ([K+]e) was set at gradually lowered values for each experiment in the series to give graded inhibition of the Na-K pump and thus graded elevation of [Na+]i. [Ca2+]e was then increased from 0 to 2 mM and the DeltaRF recorded. The results shown that increasing DeltaRF occurs with decreasing [K+]e (and thus increasing [Na+]i. Thus, not only does the Delta RF for a Delta[Ca2+]i depend on [Na+]e, but does so in a graded manner. This is further evidence for the activity of the Na/Ca exchange in controlling DeltaRF in isolated rat muscle. In extending these studies to the intact heart we hypothesized that after a Ca2+ free period the magnitude of the Na+ gradient at the onset of Ca2+ reperfusion would grade the ensuing cell Ca2+ gain. Our results indicate that (1) myocardial cell Na+ increases during Ca2+ free perfusion and (2) the magnitude of the Na+ gradient at the end of the Ca2+ free period is an important determinant of the extent of cell Ca2+ gain, cell K+ loss, and reduction of contractile function with Ca2+ reintroduction, which collectively have been referred to as the "calcium paradox" in the heart.