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The role of intracellular sodium in the regulation of NMDA-receptor-mediated channel activity and toxicity

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Abstract

Sodium (Na+) is the major cation in extracellular space and, with its entry into cells, may act as a critical intracellular second messenger that regulates many cellular functions. Through our investigations of mechanisms underlying the activity-dependent regulation of N-methyl-d-aspartate (NMDA) receptors, we recently characterized intracellular Na+ as a possible signaling factor common to processes underlying the upregulation of NMDA receptors by non-NMDA glutamate channels, voltage-gated Na+ channels, and remote NMDA receptors. Furthermore, although Ca2+ influx during the activation of NMDA receptors acts as a negative feedback mechanism that downregulates NMDA receptor activity, Na+ influx provides an essential positive feedback mechanism to overcome Ca2+-induced inhibition, thereby potentiating both NMDA receptor activity and inward Ca2+ flow. NMDA receptors may be recruited to cause excitoxicity through a Na+-dependent mechanism. Therefore, the further characterization of mechanisms underlying the regulation of NMDA receptors by intracellular Na+ is essential to understanding activity-dependent neuroplasticity in the nervous system.

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  1. Department of Biomedical Science, College of Medicine, Florida State University, Tallahassee, FL

    Xian-Min Yu

  2. Faculty of Dentistry, University of Toronto, M5G 1G6, Toronto, Ontario, Canada

    Xian-Min Yu

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Yu, XM. The role of intracellular sodium in the regulation of NMDA-receptor-mediated channel activity and toxicity. Mol Neurobiol 33, 63–79 (2006). https://doi.org/10.1385/MN:33:1:063

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