Endoplasmic reticulum Ca²⁺ homeostasis and neuronal death

Abstract

The endoplasmic reticulum (ER) is a universal signalling organelle, which regulates a wide range of neuronal functional responses. Calcium release from the ER underlies various forms of intracellular Ca²⁺ signalling by either amplifying Ca²⁺ entry through voltage‐gated Ca²⁺ channels by Ca²⁺‐induced Ca²⁺ release (CICR) or by producing local or global cytosolic calcium fluctuations following stimulation of metabotropic receptors through inositol‐1,4,5‐trisphosphate‐induced Ca²⁺ release (IICR). The ER Ca²⁺ store emerges as a single interconnected pool, thus allowing for a long‐range Ca²⁺ signalling via intra‐ER tunnels. The fluctuations of intra‐ER free Ca²⁺ concentration regulate the activity of numerous ER resident proteins responsible for post‐translational protein folding and modification. Disruption of ER Ca²⁺ homeostasis results in the developing of ER stress response, which in turn controls neuronal survival. Altered ER Ca²⁺ handling may be involved in pathogenesis of various, neurodegenerative diseases including brain ischemia and Alzheimer dementia.