The Role of Intracellular Sodium in the Regulation of NMDA-Receptor-Mediated Channel Activity and Toxicity.
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.
Yu
Xian-Min
XM
Department of Biomedical Science, College of Medicine, Florida State University, Tallahassee, FL, USA. xianmin.yu@med.fsu.edu
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism
D015220:Calcium Channels; D007473:Ion Channels; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D012964:Sodium