Calcium Signaling IRegulation, Mechanisms, Effectors, Role in Disease and Recent Advances

Calcium (Ca2+) plays a major role in controlling cell function. It regulates life and death processes that include fertilization, cell proliferation, apoptosis and cell necrosis. It controls functional responses including muscle contraction, cell migration, secretion, metabolic pathways, gene expression and cell differentiation. The basic element of Ca2+ signalling is to... read morekeep the cytoplasmic calcium ([Ca2+]c) low and then allow selective increases in [Ca2+]c by stimulating either Ca2+ release from the cells’ internal Ca2+ stores or the influx of Ca2+ from the extracellular environment. Inside the cell, elevated Ca2+ will activate regulatory proteins (many of its actions are mediated through Ca2+-binding proteins such as calmodulin) or enter intracellular organelles where it can regulate their internal processes. Ca2+ signals are attenuated by sequestration of Ca2+ into intracellular organelles that function as Ca2+ stores or by the expulsion of Ca2+ back across the plasma membrane.

Our understanding of how Ca2+ signals are generated and propagated has developed with the aid of organic fluorescent probes that can be used to measure and visualise intracellular Ca2+. More recently, recombinant probes that can measure Ca2+, either by fluorescence or luminescence, in specific sub-cellular domains have been used. These probes are now being incorporated into transgenic animals and plants to enable in vivo imaging of intracellular and intra-organellular Ca2+. In addition, electrophysiological measurements allow detailed analysis and characterisation of Ca2+-channel properties. Ca2+ signals can be complex with some involving periodic oscillations of varying frequencies or responses that are restricted to specific regions of the cell. In some cells the Ca2+ signals are very brief, taking only milliseconds, whilst in other cells they can persist over several hours.

The application of molecular biology to Ca2+ signalling research has also opened new avenues of investigation. The molecular components of key Ca2+ signalling pathways have been identified. Consequently our understanding of Ca2+ signalling is now advancing rapidly through experimental approaches that involve the controlled expression, inhibition of expression and use of naturally occurring or engineered mutations of channels, pumps, effectors and other proteins related to Ca2+ signalling pathways.

Ca2+ signalling is an extremely active research field. This series is designed to cover the key processes that contribute to cellular Ca2+ homeostasis and includes topical issues and recent developments described by the fields’ leading scientists. Series II focuses on the rapidly expanding topic of Ca2+ and disease. It is designed to give an insight into the broad range of pathologies that involve a disturbance of Ca2+ signalling.