Swietach Pawel, Leem Chae-Hun, Spitzer Kenneth W, Vaughan-Jones Richard D
Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, Oxford, UK
Department of Physiology, University of Ulsan College of Medicine, Seoul, Republic of Korea.
J Physiol. 2014 Aug 1;592(15):3179-88. doi: 10.1113/jphysiol.2013.265959. Epub 2014 Feb 10.
Cellular processes are exquisitely sensitive to H+ and Ca2+ ions because of powerful ionic interactions with proteins. By regulating the spatial and temporal distribution of intracellular [Ca2+] and [H+], cells such as cardiac myocytes can exercise control over their biological function. A well-established paradigm in cellular physiology is that ion concentrations are regulated by specialized, membrane-embedded transporter proteins. Many of these couple the movement of two or more ionic species per transport cycle, thereby linking ion concentrations among neighbouring compartments. Here, we compare and contrast canonical membrane transport with a novel type of Ca(2+)-H+ coupling within cytoplasm, which produces uphill Ca2+ transport energized by spatial H+ ion gradients, and can result in the cytoplasmic compartmentalization of Ca2+ without requiring a partitioning membrane. The mechanism, demonstrated in mammalian myocytes, relies on diffusible cytoplasmic buffers, such as carnosine, homocarnosine and ATP, to which Ca2+ and H+ ions bind in an apparently competitive manner. These buffer molecules can actively recruit Ca2+ to acidic microdomains, in exchange for the movement of H+ ions. The resulting Ca2+ microdomains thus have the potential to regulate function locally. Spatial cytoplasmic Ca(2+)-H+ exchange (cCHX) acts like a 'pump' without a membrane and may be operational in many cell types.
由于与蛋白质存在强大的离子相互作用，细胞过程对H⁺和Ca²⁺离子极为敏感。通过调节细胞内[Ca²⁺]和[H⁺]的空间和时间分布，心肌细胞等细胞能够控制其生物学功能。细胞生理学中一个公认的范式是，离子浓度由专门的膜嵌入转运蛋白调节。其中许多转运蛋白在每个运输周期中耦合两种或更多种离子的移动，从而将相邻隔室之间的离子浓度联系起来。在这里，我们将经典的膜运输与细胞质中一种新型的Ca²⁺-H⁺耦合进行比较和对比，这种耦合产生由空间H⁺离子梯度驱动的上坡Ca²⁺运输，并可导致Ca²⁺在细胞质中的区室化，而无需分隔膜。在哺乳动物心肌细胞中证明的这种机制依赖于可扩散的细胞质缓冲剂，如肌肽、高肌肽和ATP，Ca²⁺和H⁺离子以明显竞争的方式与它们结合。这些缓冲分子可以将Ca²⁺主动募集到酸性微区，以交换H⁺离子的移动。由此产生的Ca²⁺微区因此具有局部调节功能的潜力。空间细胞质Ca²⁺-H⁺交换（cCHX）的作用类似于没有膜的“泵”，可能在许多细胞类型中起作用。
