Chondroitin sulfate, a major component of the perineuronal net, elicits inward currents, cell depolarization, and calcium transients by acting on AMPA and kainate receptors of hippocampal neurons

Abstract

Chondroitin sulfate (CS) proteoglycans (CSPGs) are the most abundant PGs of the brain extracellular matrix (ECM). Free CS could be released during ECM degradation and exert physiological functions; thus, we aimed to investigate the effects of CS on voltage- and current-clamped rat embryo hippocampal neurons in primary cultures. We found that CS elicited a whole-cell Na+- dependent inward current (ICS) that produced drastic cell depolarization, and a cytosolic calcium transient ([Ca2+] c). Those effects were similar to those elicited by α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and kainate, were completely blocked by NBQX and CNQX, were partially blocked by GYKI, and were unaffected by MK801 and D-APV. Furthermore, ICS and AMPA currents were similarly potentiated by cyclothiazide, a positive allosteric modulator of AMPA receptors. Because CSPGs have been attributed Ca2+ -dependent roles, such as neural network development, axon pathfinding, plasticity and regeneration after CNS injury, CS action after ECM degradation could be contributing to the mediation of these effects through its interaction with AMPA and kainate receptors. Chondroitin sulfate (CS) may not play a simple role as a major component of proteoglycans (CSPGs) of extracellular matrix and perineural net (ECM/PNN). We present evidence to suggest that free CS, coming from CSPGs degradation, could play a relevant functional role in the regulation of hippocampal neurotransmission and synaptic plasticity, through the activation of an inward Na+-dependent current (ICS) that causes membrane depolarization (Em) and a cytosolic Ca2+ transient. © 2013 International Society for Neurochemistry.