Heterogeneity of GABA(A) receptor-mediated responses in the human IMR-32 neuroblastoma cell line

The gamma-aminobutyric acid (GABA) response profiles of IMR-32 human neurob lastoma cells were examined using whole-cell patch clamp and RT-PCR techniq ues. GABA activated a concentration-dependent and bicuculline-sensitive cur rent, and RT-PCR revealed the expression of multiple GABA, receptor subunit mRNAs (alpha(1), alpha(3), alpha(4), beta(1), beta(3), gamma(2), and delta ). A pharmacological profile of the GABA-induced current was derived using several subunit-selective agents. Diazepam, which requires the presence of a gamma subunit in order to modulate GABA(A) receptor-mediated responses, p otentiated GABA-induced currents in a subset of IMR-32 cells. Two populatio ns of GABA-activated currents were also evident based on sensitivity to mod ulation by zinc. Comparison of zinc- and diazepam-induced modulation of GAB A-induced current responses in the same cells revealed an inverse correlati on between these two modulators. No differences, however, were observed wit h the GABA(A) receptor modulators loreclezole, allopregnanolone, and pentob arbital. Thus, IMR-32 cells maintained in culture are heterogeneous in term s of expression of GABA(A) receptor isoforms. (C) 2000 Wiley-Liss, Inc.