Sodium homeostasis in rat hippocampal slices during oxygen and glucose deprivation: Role of voltage-sensitive sodium channels

The breakdown in brain ionic homeostasis during energy deprivation (anoxic depolarization [AD]) is intimately linked to neuronal injury. We studied the role of one particular route of Na + influx, voltage-sensitive Na + channels, in the AD induced by O 2 and/or glucose deprivation. We recorded extracellular Na + concentration ([Na +](e)) and direct current potential (DCP) in the CA1 stratum pyramidale of hippocampal slices using Na +-selective microelectrodes. Tetrodotoxin (0.1-1 μM) delayed the occurrence of AD and reduced the peak change in both [Na +](e) and DCP during AD. However the tetrodotoxin effects were overcome by a concomitant reduction in extracellular glucose during anoxia. We conclude that: (1) the activation of voltage-gated Na + channels is involved in the triggering of AD; (2) there may be a critical level of energy depletion when AD occurs and different mechanisms may underlie AD during hypoxia, compared to O 2 and glucose deprivation. Copyright (C) 1999 Elsevier Science Ireland Ltd.link_to_subscribed_fulltex

Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence.

Arc is an activity-regulated neuronal protein, but little is known about its interactions, assembly into multiprotein complexes, and role in human disease and cognition. We applied an integrated proteomic and genetic strategy by targeting a tandem affinity purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice. This allowed biochemical and proteomic characterization of native complexes in wild-type and knockout mice. We identified many Arc-interacting proteins, of which PSD95 was the most abundant. PSD95 was essential for Arc assembly into 1.5-MDa complexes and activity-dependent recruitment to excitatory synapses. Integrating human genetic data with proteomic data showed that Arc-PSD95 complexes are enriched in schizophrenia, intellectual disability, autism, and epilepsy mutations and normal variants in intelligence. We propose that Arc-PSD95 postsynaptic complexes potentially affect human cognitive function