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

Author: Yu, Xian-Min

Source: Molecular Neurobiology, Volume 33, Number 1, February 2006 , pp. 63-79(17)

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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.

Keywords: NMDA channel gating; sodium and calcium; single-channel activity; excitability; toxicity

Document Type: Research article

DOI: http://dx.doi.org/10.1385/MN:33:1:063

Affiliations: 1: Department of Biomedical Science, College of Medicine, Florida State University, Tallahassee, FL, Email: xianmin.yu@med.fsu.edu

Publication date: 2006-02-01