Pumping Ca² up H gradients: a Ca²-H exchanger without a membrane.

Swietach, Pawel; Leem, Chae‐Hun; Spitzer, Kenneth W.; Vaughan‐Jones, Richard D.

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 Ca2 -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 Ca2 -H exchange (cCHX) acts like a 'pump' without a membrane and may be operational in many cell types.

CELL communication; CALCIUM ions; HYDROGEN ions; MUSCLE cells; MEMBRANE transport proteins; PHYSIOLOGY

Journal of Physiology, 2014, Vol 592, Issue 15, p3179

0022-3751

Academic Journal

10.1113/jphysiol.2013.265959