Calcium Signalling and Regulation of Cell Function


The calcium ion (Ca2+) is a versatile intracellular messenger. It provides dynamic regulation of vast array of cellular processes such as gene transcription, differentiation and contraction. Ca2+ signals range from microsecond, nanoscopic events to intercellular waves lasting for many seconds. This diversity of Ca2+ signals arises from the wide assortment of Ca2+ transport and Ca2+ buffering processes employed by cells. Additional diversity in Ca2+ signalling stems from the ability of cells to utilise different sources of Ca2+. The cytosol is the principal Ca2+ signalling compartment. When Ca2+ ions enter the cytosol they interact with numerous Ca2+‐binding proteins, thereby leading to activation, or inhibition, of cellular processes. Specificity is achieved by regulating the spatial and kinetic properties of Ca2+ signal. In this way, many concurrent Ca2+‐sensitive cellular processes can be discretely regulated. A number of pathologies have been related to the breakdown of cellular Ca2+ homoeostasis or to aberrant Ca2+ signalling.

Key Concepts:

  • Calcium is a critical intracellular signal that controls key cell fate decisions.

  • Calcium signals derive from multiple sources that are accessed by a diverse range of transport mechanisms.

  • The kinetics and spatial properties of calcium signals determine their impact on cellular activity.

  • Ca2+ signals are tissue‐specific and are appropriate to regulate the physiological functions of individual cell types.

Keywords: calcium; signalling; channel; homoeostasis; ion

Figure 1.

Ca2+ oscillations and Ca2+ waves. (a) Depicts Ca2+ oscillations in a single HeLa cell (an epithelial cell line) that was stimulated with the InsP3‐generating agonist histamine. The cytosolic Ca2+ concentration was monitored using a Ca2+‐sensitive fluorescent indicator (Fura2). As the panel indicates, application of histamine evoked Ca2+ oscillations. The frequency of the oscillations increased with the higher histamine concentration. (b) Shows a montage of images depicting a Ca2+ wave travelling across a single cell. Several cells are shown within the images. One of the cells (right‐hand side) has already responded. A Ca2+ wave can be seen to develop in the cell at the bottom. The nuclei of the responding cells appear very bright in these images. Ca2+‐sensitive fluorescent indicators have enhanced fluorescence in the nucleus for reasons that are not understood. (c) Illustrates the time course of the Ca2+ wave travelling through the cell. The three traces were recorded from the sub‐cellular regions depicted in the last image of (b). The wave starts in the right‐hand side of the cell (region indicated by black circle and black trace), and then travels through the rest of the cell.

Figure 2.

Ca2+ ‘on’ and ‘off’ mechanisms. This figure represents a summary of processes that modulate cytoplasmic Ca2+ levels. The Ca2+ ‘on’ mechanisms responsible for increasing cytosolic Ca2+ are marked by red arrows, and the Ca2+ ‘off’ mechanisms are shown in blue. A dynamic interplay of these processes determines the spatio‐temporal characteristics of a Ca2+ signal. See the text for details. Plasma membrane Ca2+ATPase, PMCA; sarcoplamic/endoplasmic reticulum Ca2+ATPase, SERCA.

Figure 3.

Mechanisms of Ca2+ release. (a)–(f) Depict some of the known mechanisms underlying Ca2+ release from intracellular Ca2+ stores. (a), (b) and (c) illustrate the activation of RyRs in skeletal muscle, cardiac muscle/neurons and in cells utilising cADPR, respectively. (d) Shows the release of Ca2+ by NAADP from two‐pore channels. Ca2+ release via InsP3Rs or sphingosine‐1‐phosphate (S‐1‐P) receptors are depicted in (e) and (f), respectively.

Figure 4.

Elementary and global Ca2+ signals in a single cardiac myocyte. The figure depicts Ca2+ signals recorded using laser scanning confocal microscopy of a single cardiac myocyte. (a) Illustrates a single elementary Ca2+ signal (a ‘Ca2+ spark’), which occurred spontaneously when the cell was not electrically stimulated. (b) Depicts a global increase in Ca2+ seen following an action potential. Such global Ca2+ signals are constructed by the recruitment and spatial summation of many elementary Ca2+ release signals. The images in (a) and (b) were obtained from the same cell.



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Further reading

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Roderick HL, Berridge MJ and Bootman MD (2003) Calcium‐induced calcium release. Current Biology 13: R425.

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Bootman, Martin D, Rietdorf, Katja, Hardy, Holly, Dautova, Yana, Corps, Elaine, Pierro, Cristina, Stapleton, Eloise, Kang, Esther, and Proudfoot, Diane(Oct 2012) Calcium Signalling and Regulation of Cell Function. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001265.pub3]