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 neuroblastoma cells were examined using whole-cell patch clamp and RT-PCR techniques. GABA activated a concentration-dependent and bicuculline-sensitive current, and RT-PCR revealed the expression of multiple GABA(A) 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, potentiated GABA-induced currents in a subset of IMR-32 cells. Two populations of GABA-activated currents were also evident based on sensitivity to modulation by zinc. Comparison of zinc- and diazepam-induced modulation of GABA-induced current responses in the same cells revealed an inverse correlation between these two modulators. No differences, however, were observed with the GABA(A) receptor modulators loreclezole, allopregnanolone, and pentobarbital. Thus, IMR-32 cells maintained in culture are heterogeneous in terms of expression of GABA(A) receptor isoforms.
Sapp
D W
DW
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030, USA.
Yeh
H H
HH
D000927:Anticonvulsants / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018757:GABA Modulators / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014230:Triazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D000927:Anticonvulsants; D018757:GABA Modulators; D020033:Protein Isoforms; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D014230:Triazoles; D005680:gamma-Aminobutyric Acid; C066440:loreclezole; D011280:Pregnanolone; D010424:Pentobarbital; D015032:Zinc; D003975:Diazepam; D001640:Bicuculline