Capacitative calcium entry in the nervous system

Capacitative calcium entry is a process whereby the depletion of Ca 2+ from intracellular stores (likely endoplasmic or sarcoplasmic reticulum) activates plasma membrane Ca 2+ channels. Current research has focused on identification of capacitative calcium entry channels and the mechanism by which Ca 2+ store depletion activates the channels. Leading candidates for the channels are members of the transient receptor potential (TRP) superfamily, although no single gene or gene product has been definitively proven to mediate capacitative calcium entry. The mechanism for activation of the channels is not known; proposals fall into two general categories, either a diffusible signal released from the Ca 2+ stores when their Ca 2+ levels become depleted, or a more direct protein–protein interaction between constituents of the endoplasmic reticulum and the plasma membrane channels. Capacitative calcium entry is a major mechanism for regulated Ca 2+ influx in non-excitable cells, but recent research has indicated that this pathway plays an important role in the function of neuronal cells, and may be important in a number of neuropathological conditions. This review will summarize some of these more recent findings regarding the role of capacitative calcium entry in normal and pathological processes in the nervous system.