The Ca2+/calmodulin system in neuronal hyperexcitability

Calmodulin (CaM) is a major Ca2+-binding protein in the brain, where it pla ys an important role in the neuronal response to changes in the intracellul ar Ca2+ concentration. Calmodulin modulates numerous Ca2+-dependent enzymes and participates in relevant cellular functions. Among the different CaM-b inding proteins, the Ca2+/CaM dependent protein kinase II and the phosphata se calcineurin are especially important in the brain because of their abund ance and their participation in numerous neuronal functions. Therefore, the role of the Ca2+/CaM signalling system in different neurotoxicological or neuropathological conditions associated to alterations in the intracellular Ca2+ concentration is a subject of interest. We here report different evid ences showing the involvement of CaM and the CaM-binding proteins above men tioned in situations of neuronal hyperexcitability induced by convulsant ag ents. Signal transduction pathways mediated by specific CaM binding protein s warrant future study as potential targets in the development of new drugs to inhibit convulsant responses or to prevent or attenuate the alterations in neuronal function associated to the deleterious increases in the intrac ellular Ca2+ levels described in different pathological situations. (C) 200 1 Elsevier Science Ltd. All rights reserved.