Several generations of cardiac physiologists have verified that basal cardiac contractility depends strongly on the transsarcolemmal Na gradient, and the underlying molecular mechanisms that link cardiac excitation-contraction coupling (ECC) to the Na gradient have been elucidated in good detail for more than 30 years. In brief, small increases of cytoplasmic Na push cardiac (NCX1) Na/Ca exchangers to increase contractility by increasing the myocyte Ca load. Accordingly, basal cardiac contractility is expected to be physiologically regulated by pathways that modify the cardiac Na gradient and the function of Na transporters. Assuming that this expectation is correct, it remains to be elucidated how in detail signaling pathways affecting the cardiac Na gradient are controlled in response to changing cardiac output requirements. Some puzzle pieces that may facilitate progress are outlined in this short review. Key open issues include (1) whether the concept of local Na gradients is viable, (2) how in detail Na channels, Na transporters and Na/K pumps are regulated by lipids and metabolic processes, (3) the physiological roles of Na/K pump inactivation, and (4) the possibility that key diffusible signaling molecules remain to be discovered.

中文翻译：

---

通过钠控制心脏收缩：承诺，推论和新的开始。

几代心脏生理学家已经证实，基础心脏的收缩力在很大程度上取决于跨肌膜Na梯度，并且将心脏兴奋-收缩偶联（ECC）与Na梯度联系起来的潜在分子机制已被详细阐明了30多年。简而言之，胞质钠推动心脏（NCX1）Na / Ca交换子的少量增加通过增加心肌细胞Ca负荷来增加收缩力。因此，预期通过改变心脏Na梯度和Na转运蛋白功能的途径在生理上调节基础心脏收缩力。假定这种期望是正确的，则有待阐明如何响应于变化的心输出量来详细控制影响心脏Na梯度的信号传导途径。这篇简短的评论概述了一些可能有助于进步的难题。尚未解决的主要问题包括：（1）局部Na梯度的概念是否可行；（2）脂质和代谢过程如何详细调节Na通道，Na转运蛋白和Na / K泵；（3）Na / K泵失活，以及（4）关键扩散信号分子仍有待发现的可能性。