PT  - JOURNAL ARTICLE
AU  - Jean-Marie Mangin
AU  - Laurent Nguyen
AU  - Catherine Gougnard
AU  - Grégory Hans
AU  - Bernard Rogister
AU  - Shibeshih Belachew
AU  - Gustave Moonen
AU  - Pascal Legendre
AU  - Jean-Michel Rigo
TI  - Developmental Regulation of β-Carboline-Induced Inhibition of Glycine-Evoked Responses Depends on Glycine Receptor β Subunit Expression
AID  - 10.1124/mol.104.007435
DP  - 2005 May 01
TA  - Molecular Pharmacology
PG  - 1783--1796
VI  - 67
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/67/5/1783.short
4100  - http://molpharm.aspetjournals.org/content/67/5/1783.full
SO  - Mol Pharmacol2005 May 01; 67
AB  - In this work, we show that β-carbolines, which are known negative allosteric modulators of GABAA receptors, inhibit glycine-induced currents of embryonic mouse spinal cord and hippocampal neurons. In both cell types, β-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 β-carboline inhibition of glycine responses and high conductance levels is almost complete in mature neurons, whereas a weaker decrease in β-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 β-carbolines depends on β subunit expression, Chinese hamster ovary cells were permanently transfected either with GlyR α2 subunit alone or in combination with GlyR β subunit. Single-channel recordings revealed that the major conductance levels shifted from high levels (≥50 pS) in GlyR-α2-transfected cells to low levels (<50 pS) in GlyR-α2+β-containing cells. Consistently, both picrotoxin- and β-carboline-induced inhibition of glycine-gated currents were significantly decreased in GlyR-α2+β-transfected cells compared with GlyR-α2-containing cells. In summary, we demonstrate that the incorporation of β subunits in GlyRs confers resistance not only to picrotoxin but also to β-carboline-induced inhibition. Furthermore, we also provide evidence that hippocampal neurons undergo in vitro a partial maturation process of their GlyR-mediated responses.