Recognition molecule associated carbohydrate inhibits postsynaptic GABAB receptors:: a mechanism for homeostatic regulation of GABA release in perisomatic synapses

Extracellular matrix molecules are important cues in the shaping of nervous system structure and function. Here, we describe a novel mechanism by which the HNK-1 carbohydrate carried by recognition molecules regulates perisomatic inhibition in the hippocampus. Neutralization of HNK-1 activity by an HNK-1 antibody results in GABA(B) receptor-mediated activation of K+ currents in CA1 pyramidal cells, which elevates extracellular K+ concentration and reduces evoked GAGA release in perisomatic inhibitory synapses. This mechanism is supported by pharmacological analysis in hippocampal slices and data showing that the HNK-1 carbohydrate binds to GABA(B) receptors and inhibits GABA(B) receptor-activated K+ currents in a heterologous expression system. We suggest that the HNK-1 carbohydrate is involved in homeostatic regulation of GABA(A) receptor-mediated perisomatic inhibition by suppression of postsynaptic GABAB receptor activity. (C) 2003 Elsevier Science (USA). All rights reserved.