Neuronal Store-Operated Calcium Channels

The endoplasmic reticulum (ER) is the major intracellular calcium (Ca²⁺) storage compartment in eukaryotic cells. In most instances, the mobilization of Ca²⁺ from this store is followed by a delayed and sustained uptake of Ca²⁺ through Ca²⁺-permeable channels of the cell surface named store-operated Ca²⁺ channels (SOCCs). This gives rise to a store-operated Ca²⁺ entry (SOCE) that has been thoroughly investigated in electrically non-excitable cells where it is the principal regulated Ca²⁺ entry pathway. The existence of this Ca²⁺ route in neurons has long been a matter of debate. However, a growing body of experimental evidence indicates that the recruitment of Ca²⁺ from neuronal ER Ca²⁺ stores generates a SOCE. The present review summarizes the main studies supporting the presence of a depletion-dependent Ca²⁺ entry in neurons. It also addresses the question of the molecular composition of neuronal SOCCs, their expression, pharmacological properties, as well as their physiological relevance.