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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/1000

Title: Developmental regulation of beta-carboline-induced inhibition of glycine-evoked responses depends on glycine receptor beta subunit expression
Authors: MANGIN, Jean-Marie
Nguyen, L.
Gougnard, C.
Rogister, B.
Belachew, S.
Moonen, G.
RIGO, Jean-Michel
Issue Date: 2005
Publisher: Bethesda : AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Citation: MOLECULAR PHARMACOLOGY, 67(5). p. 1783-1796
Abstract: In this work, we show that beta-carbolines, which are known negative allosteric modulators of GABA A receptors, inhibit glycine-induced currents of embryonic mouse spinal cord and hippocampal neurons. In both cell types, beta-carboline-induced inhibition of glycine receptor (GlyR)-mediated responses decreases with time in culture. Single-channel recordings show that the major conductance levels of GlyR unitary currents shifts from high levels (>= 50 pS) in 2 to 3 days in vitro (DIV) neurons to low levels (< 50 pS) in 11 to 14 DIV neurons, assessing the replacement of functional homomeric GlyR by heteromeric GlyR. In cultured spinal cord neurons, the disappearance of beta-carboline inhibition of glycine responses and high conductance levels is almost complete in mature neurons, whereas a weaker decrease in beta-carboline-evoked glycine response inhibition and high conductance level proportion is observed in hippocampal neurons. To confirm the hypothesis that the decreased sensitivity of GlyR to beta-carbolines depends on beta subunit expression, Chinese hamster ovary cells were permanently transfected either with GlyR alpha 2 subunit alone or in combination with GlyR beta subunit. Single-channel recordings revealed that the major conductance levels shifted from high levels (>= 50 pS) in GlyR-alpha 2-transfected cells to low levels (< 50 pS) in GlyR-alpha 2-containing cells. Consistently, both picrotoxinand beta-carboline-induced inhibition of glycine-gated currents were significantly decreased in GlyR-alpha 2-transfected cells compared with GlyR-alpha 2-containing cells. In summary, we demonstrate that the incorporation of beta subunits in GlyRs confers resistance not only to picrotoxin but also to beta-carbolineinduced inhibition. Furthermore, we also provide evidence that hippocampal neurons undergo in vitro a partial maturation process of their GlyR-mediated responses.
URI: http://hdl.handle.net/1942/1000
DOI: 10.1124/mol.104.007435
ISI #: 000228387900048
ISSN: 0026-895X
Category: A1
Type: Journal Contribution
Validation: ecoom, 2006
Appears in Collections: Research publications

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