Calcium as an extracellular signalling molecule: perspectives on the Calcium Sensing Receptor in the brain

Calcium acts as a universal signal that is responsible for controlling a spectrum of cellular processes ranging from fertilization to apoptosis. For a long time, calcium was regarded solely as an intracellular second messenger. However, the discovery that calcium can also act as an external ligand together with the molecular cloning of its cell surface receptor, the Calcium Sensing Receptor (CaSR), demonstrated that calcium also acts as an important extracellular or first messenger. Here, we give an overview of the main structural, pharmacological and physiological features of the CaSR and provide an assessment of its functions and cellular and molecular mechanisms of action. In addition, we propose possible avenues for future research into the trafficking of CaSR and the role(s) of this receptor in the central nervous system.