Recognition molecule associated carbohydrate inhibits postsynaptic GABA(B) 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 GABA 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 GABA(B) receptor activity.
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, 20246 Hamburg, Germany.
Armen K
AK
Saghatelyan
Marina
M
Snapyan
Silke
S
Gorissen
Inge
I
Meigel
Johannes
J
Mosbacher
Klemens
K
Kaupmann
Bernhard
B
Bettler
Andrei V
AV
Kornilov
Nikolay E
NE
Nifantiev
Vehary
V
Sakanyan
Melitta
M
Schachner
Alexander
A
Dityatev
D000818:Animals; D018959:CD57 Antigens / Q000378:metabolism*; D002460:Cell Line; D006624:Hippocampus / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018959:CD57 Antigens; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid