Reference : Developmental regulation of beta-carboline-induced inhibition of glycine-evoked response...
Scientific journals : Article
Life sciences : Anatomy (cytology, histology, embryology...) & physiology
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/4923
Developmental regulation of beta-carboline-induced inhibition of glycine-evoked responses depends on glycine receptor beta subunit expression
English
Mangin, Jean-Marie [> > > >]
Nguyen, Laurent mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie >]
Gougnard, Catherine [> > > >]
Hans, Grégory mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anesthésie et réanimation >]
Rogister, Bernard mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine >]
Belachew, Shibeshih mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie >]
Moonen, Gustave mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie - Doyen de la Faculté de Médecine]
Legendre, Pascal [> > > >]
Rigo, Jean-Michel [Universiteit Hasselt - UH > > > >]
May-2005
Molecular Pharmacology
Amer Soc Pharmacology Experimental Therapeutics
67
5
1783-1796
Yes (verified by ORBi)
International
0026-895X
Bethesda
[en] glycine ; beta carboline ; electrophysiology
[en] 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.
Researchers ; Students
http://hdl.handle.net/2268/4923
10.1124/mol.104.007435

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