GABA(A) receptor beta3 subunit deletion decreases alpha2/3 subunits and IPSC duration.
Deletion of the beta3 subunit of the GABA(A) receptor produces severe behavioral deficits and epilepsy. GABA(A) receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in cortical neurons in cultures from beta3 -/- mice were significantly faster than those in beta3 +/+ mice and were more prolonged by zolpidem. Surface staining revealed that the number of beta2/3, alpha2, and alpha3 (but not of alpha1) subunit-expressing neurons and the intensity of subunit clusters were significantly reduced in beta3 -/- mice. Transfection of beta3 -/- neurons with beta3 cDNA restored beta2/3, alpha2, and alpha3 subunits immunostaining and slowed mIPSCs decay. We show that the deletion of the beta3 subunit causes the loss of a subset of GABA(A) receptors with alpha2 and alpha3 subunits while leaving a receptor population containing predominantly alpha1 subunit with fast spontaneous IPSC decay and increased zolpidem sensitivity.
Ramadan
Epolia
E
Department of Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.
Fu
Zhanyan
Z
Losi
Gabriele
G
Homanics
Gregg E
GE
Neale
Joseph H
JH
Vicini
Stefano
S
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D017353:Gene Deletion; D015870:Gene Expression / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016296:Mutagenesis / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D000077334:Zolpidem
D018755:GABA Agonists; D011725:Pyridines; D011963:Receptors, GABA-A; D000077334:Zolpidem