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.