薬物代謝と毒性学ジャーナル
オープンアクセス

概要

Critical Regulation of Calcium Signaling and NMDA-type Glutamate Receptor In Developmental Neural Toxicity

Cheng Wang

Calcium (Ca2+) is a vital element in the process of neurotransmitter release, and is a common signaling mechanism. Calcium can act in signal transduction after influx resulting from activation of ion channels or as a second messenger. Glutamate receptors play an important role in the excitatory synaptic action of the central nervous system. Activation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor increases the concentration of (Ca2+) in the cell. Ca2+ can in turn function as a second messenger in various signaling pathways. The developing nervous system varies in susceptibility to neurotoxic insults depending on the stage of development. By monitoring alterations in calcium influx, cell signaling processes, expression levels of receptor subtypes and imaging outcomes, it may be possible to completely define the affected system(s) during development. This review attempts to discuss how the potential application of some sophisticated research approaches, e.g., calcium imaging/Ca2+ influx and monitoring gene and/or protein expression levels of receptor subtypes, provides a platform in which preclinical research models can inform clinical interventions and vice versa in the developing brain. This review focuses the discussion on representative general anesthetic agents - primarily ketamine - as examples of how the Ca2+ influx event and specific receptor subunit expression can be used to dissect relevant mechanisms underlying the etiology of the neurotoxicity associated with developmental exposures to anesthetic agents.