Pumping Ca<sup>2+</sup> up H<sup>+</sup> gradients: A Ca<sup>2+</sup>-H<sup>+</sup> exchanger without a membrane
Swietach P., Leem CH., Spitzer KW., Vaughan-Jones RD.
Cellular processes are exquisitely sensitive to H + and Ca 2+ ions because of powerful ionic interactions with proteins. By regulating the spatial and temporal distribution of intracellular [Ca 2+ ] 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 Ca 2+ transport energized by spatial H + ion gradients, and can result in the cytoplasmic compartmentalization of Ca 2+ without requiring a partitioning membrane. The mechanism, demonstrated in mammalian myocytes, relies on diffusible cytoplasmic buffers, such as carnosine, homocarnosine and ATP, to which Ca 2+ and H + ions bind in an apparently competitive manner. These buffer molecules can actively recruit Ca 2+ to acidic microdomains, in exchange for the movement of H + ions. The resulting Ca 2+ 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. © 2014 The Physiological Society.