Calcium in the brain under physiological and pathological conditions

This paper reviews the role of calcium in the brain under physiological and pathological conditions. Calcium is a ubiquitous first and second messenger, and a regulator of metabolic pathways, serving the purpose of transforming external messages into the appropriate cellular metabolic responses. At least three voltage-sensitive calcium channels (L, T and N) are involved as well as agonist-operated calcium channels (AOCCs). The latter are the major contributors to postsynaptic calcium entry, the majority being gated by glutamate receptors. Intracellular release occurs from endoplasmatic reticulum and other sites (calcisomes). The calcium hypothesis of cell necrosis postulates that whenever free intracellular calcium concentrations become pathologically enhanced, calcium-activated reactions may become uncontrolled adversely altering cell functioning and disrupting cellular structures. Excessive calcium influx is now thought to occur primarily via AOCCs, more particularly those activated by glutamate.