GABAA Receptor 3 Subunit Deletion Decreases 2/3 Subunits and IPSC Duration

Ramadan, Epolia, Zhanyan Fu, Gabriele Losi, Gregg E. Homanics, Joseph H. Neale, and Stefano Vicini. GABAA receptor 3 subunit deletion decreases 2/3 subunits and IPSC duration. J Neurophysiol 89: 128–134, 2003. 10.1152/jn.00700.2002. Deletion of the 3 subunit of the GABAA receptor produces severe behavioral deficits and epilepsy. GABAA receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in cortical neurons in cultures from 3 / mice were significantly faster than those in 3 / mice and were more prolonged by zolpidem. Surface staining revealed that the number of 2/3, 2, and 3 (but not of 1) subunit-expressing neurons and the intensity of subunit clusters were significantly reduced in 3 / mice. Transfection of 3 / neurons with 3 cDNA restored 2/3, 2, and 3 subunits immunostaining and slowed mIPSCs decay. We show that the deletion of the 3 subunit causes the loss of a subset of GABAA receptors with 2 and 3 subunits while leaving a receptor population containing predominantly 1 subunit with fast spontaneous IPSC decay and increased zolpidem sensitivity.