Intracellular Calcium Homeostasis and Signaling

  • Marisa BriniEmail author
  • Tito Calì
  • Denis Ottolini
  • Ernesto CarafoliEmail author
Part of the Metal Ions in Life Sciences book series (MILS, volume 12)


Ca2+ is a universal carrier of biological information: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca2+ is a conventional diffusible second messenger released inside cells by the interaction of first messengers with plasma membrane receptors. However, it can also penetrate directly into cells to deliver information without the intermediation of first or second messengers. Even more distinctively, Ca2+ can act as a first messenger, by interacting with a plasma membrane receptor to set in motion intracellular signaling pathways that involve Ca2+ itself. Perhaps the most distinctive property of the Ca2+ signal is its ambivalence: while essential to the correct functioning of cells, Ca2+ becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully tuned. Ca2+ is controlled by reversible complexation to specific proteins, which could be pure Ca2+ buffers, or which, in addition to buffering Ca2+, also decode its signal to pass it on to targets. The most important actors in the buffering of cell Ca2+ are proteins that transport it across the plasma membrane and the membrane of the organelles: some have high Ca2+ affinity and low transport capacity (e.g., Ca2+ pumps), others have opposite properties (e.g., the Ca2+ uptake system of mitochondria). Between the initial event of fertilization, and the terminal event of programmed cell death, the Ca2+ signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels.


apoptosis calcium calcium buffering proteins calcium sensor proteins calmodulin fertilization gene expression ion pumps mitochondria protein dephosphorylation protein phosphorylation Please cite as: Met. Ions Life Sci. 12 (2013) 119–168 



2-amino-3-hydroxyl-5-ethyl-4-isoxazolepropionic acid


adenosine 5’-triphosphate


cyclic adenosine diphosphate ribose




calmodulin dependent kinase


cyclic adenosine monophosphate


calcium receptor


Ca2+-binding domain


Ca2+-induced Ca2+ release


Ca2+-release activated current


cAMP response element binding


dihydropyridine receptor


downstream regulatory element


downstream regulatory element


endoplasmic reticulum


Golgi apparatus


γ-amino butyric acid


glutamate receptor


inner mitochondrial membrane


intermembrane space


inositol 1,4,5-trisphosphate


inositol 1,4,5-trisphosphate receptor




mitochondrial Ca2+ overload


mitochondrial Ca2+ uniporter


mitochondrial calcium uptake 1


mitochondrial permeability transition


nicotinic acid adenine dinucleotide phosphate


nicotinamide adenosine diphosphate


mitochondrial Na+/Ca2+ exchanger


Na+/Ca2+ exchanger


nuclear factor of activated T cells


Na+/H+ exchanger




outer mitochondrial membrane


pheochromcytoma cells


phosphatidylinositol 4,5-bisphosphate


protein kinase A


protein kinase C


phospholipase C


plasma membrane


plasma membrane Ca2+-ATPase


permeability transition pore




receptor operated Ca2+ channels


reactive oxygen species


ruthenium red


ryanodine receptor


sarco/endoplasmic reticulum Ca2+-ATPase


solute carrier


synaptosomal-associated protein 25


soluble NSF attachment protein receptor


single nucleotide polymorphism


store operated Ca2+ entry channels


secretory pathway Ca2+ ATPase


sarcoplasmic reticulum


sensors stromal interaction molecule




two pore channel


transient receptor potential channels


vesicle associate membrane protein


voltage operated Ca2+-channels



The original work by the authors has been supported over the years by grants from the Italian Ministry of University and Research (FIRB2001 to E.C., PRIN 2003, 2005 and 2008 to M.B), the Telethon Foundation (Project GGP04169 to M.B.), the FP6 program of the European Union (FP6 Network of Excellence NeuroNe, LSH-2003-2.1.3-3 to E.C. and Integrated Project Eurohear to E.C.), the Human Frontier Science Program Organization to E.C., the ERANet- Neuron (nEUROsyn), and CARIPARO Foundation to E.C, the Italian National Research Council (CNR) and the University of Padova (Progetto di Ateneo 2008 CPDA082825) to M.B.


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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Comparative Biomedicine and Food SciencesUniversity of PadovaPadovaItaly
  2. 2.Department of Biomedical SciencesUniversity of PadovaPadovaItaly
  3. 3.Venetian Institute of Molecular Medicine (VIMM)PadovaItaly

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