Department of Molecular Physiology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan.
J Mol Cell Cardiol. 2013 Aug;61:68-76. doi: 10.1016/j.yjmcc.2013.02.007. Epub 2013 Feb 18.
The Na(+) gradient produced across the cardiac sarcolemma by the ATP-dependent Na(+)-pump is a constant source of energy for Na(+)-dependent transporters. The plasma membrane Na(+)/H(+) exchanger (NHE) is one such secondary active transporter, regulating intracellular pH, Na(+) concentration, and cell volume. NHE1, the major isoform found in the heart, is activated in response to a variety of stimuli such as hormones and mechanical stress. This important characteristic of NHE1 is intimately linked to heart diseases, including maladaptive cardiac hypertrophy and subsequent heart failure, as well as acute ischemic-reperfusion injury. NHE1 activation results in elevation of pH and intracellular Na(+) concentration, which potentially enhance downstream signaling cascades in the myocardium. Therefore, in addition to determining the mechanism underlying regulation of NHE1 activity, it is important to understand how the ionic signal produced by NHE1 is transmitted to the downstream targets. Extensive studies have identified many accessory factors that interact with NHE1. Here, we have summarized the recent progress on understanding the molecular mechanism underlying NHE1 regulation and have shown a possible signaling pathway leading to cardiac remodeling, which is initiated from NHE1. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".
由 ATP 依赖的钠泵在心肌细胞膜上产生的 Na+梯度为 Na+依赖性转运蛋白提供了恒定的能量来源。质膜 Na+/H+交换器（NHE）就是这样一种次级主动转运蛋白，它可以调节细胞内 pH 值、Na+浓度和细胞体积。NHE1 是心脏中主要的同工酶，它可以响应多种刺激，如激素和机械应激而被激活。NHE1 的这一重要特性与心脏疾病密切相关，包括适应性心肌肥厚和随后的心力衰竭以及急性缺血再灌注损伤。NHE1 的激活导致 pH 值和细胞内 Na+浓度升高，这可能增强心肌中的下游信号级联反应。因此，除了确定 NHE1 活性调节的机制外，了解由 NHE1 产生的离子信号如何传递到下游靶标也很重要。大量研究已经确定了许多与 NHE1 相互作用的辅助因子。在这里，我们总结了近年来对 NHE1 调节的分子机制的理解，并展示了一条可能的信号通路，该通路从 NHE1 开始引发心脏重构。本文是题为“心肌细胞中的 Na+调节”的特刊的一部分。
