Cytoplasmic Calcium Buffering: An Integrative Crosstalk

Abstract

Calcium (Ca2+) buffering is part of an integrative crosstalk between different mechanisms and elements involved in the control of free Ca2+ ions persistence in the cytoplasm and hence, in the Ca2+-dependence of many intracellular processes. Alterations of Ca2+ homeostasis and signaling from systemic to subcellular levels also play a pivotal role in the pathogenesis of many diseases. Compared with Ca2+ sequestration towards intracellular Ca2+ stores, Ca2+ buffering is a rapid process occurring in a subsecond scale. Any molecule (or binding site) with the ability to bind Ca2+ ions could be considered, at least in principle, as a buffer. However, the term Ca2+ buffer is applied only to a small subset of Ca2+ binding proteins containing acidic side-chain residues. Ca2+ buffering in the cytoplasm mainly relies on mobile and immobile or fixed buffers controlling the diffusion of free Ca2+ ions inside the cytosol both temporally and spatially. Mobility of buffers depends on their molecular weight, but other parameters as their concentration, affinity for Ca2+ or Ca2+ binding and dissociation kinetics next to their diffusional mobility also contribute to make Ca2+ signaling one of the most complex signaling activities of the cell. The crosstalk between all the elements involved in the intracellular Ca2+ dynamics is a process of extreme complexity due to the diversity of structural and molecular elements involved but permit a highly regulated spatiotemporal control of the signal mediated by Ca2+ ions. The basis of modeling tools to study Ca2+ dynamics are also presented.