Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons

The endoplasmic reticulum ( ER) is the largest single intracellular organelle, which is present in all types of nerve cells. The ER is an interconnected, internally continuous system of tubules and cisterns, which extends from the nuclear envelope to axons and presynaptic terminals, as well as to dendrites and dendritic spines. Ca2+ release channels and Ca2+ pumps residing in the ER membrane provide for its excitability. Regulated ER Ca2+ release controls many neuronal functions, from plasmalemmal excitability to synaptic plasticity. Enzymatic cascades dependent on the Ca2+ concentration in the ER lumen integrate rapid Ca2+ signaling with long-lasting adaptive responses through modifications in protein synthesis and processing. Disruptions of ER Ca2+ homeostasis are critically involved in various forms of neuropathology.