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The Journal of Neuroscience, July 1, 1998, 18(13):4993-5007

GABA_A Receptor Pharmacology and Subtype mRNA Expression in Human Neuronal NT2-N Cells

Torben R. Neelands¹, L. John Greenfield Jr², Jie Zhang^{1, 2}, R. Scott Turner^{1, 2, 4}, and Robert L. Macdonald^{1, 2, 3}

¹ Neuroscience Program and Departments of ² Neurology and ³ Physiology, University of Michigan, and ⁴ Veterans Affairs Medical Center Geriatric Research, Education, and Clinical Center, Ann Arbor, Michigan, 48104-1687

Human NT2 teratocarcinoma cells differentiate into neuron-like NT2-N cells when treated with retinoic acid. GABA evoked concentration-dependent whole-cell currents in NT2-N cells with an EC₅₀ of 21.8 µM and a Hill slope of 1.2. GABA_A receptor (GABAR) currents reversed at E_Cl and did not display voltage-dependent rectification. GABAR single channels opened in bursts to a 23 pS main conductance level and a 19 pS subconductance level, with infrequent openings to a 27 pS conductance level. Kinetic properties of the main conductance level were similar to other native and recombinant GABAR channels. Diazepam and zolpidem enhanced GABAR currents with moderate affinity, whereas methyl-6,7-dimethoxy-4-ethyl--carboline-3-carboxylate inhibited GABAR currents. Loreclezole enhanced GABAR currents with high affinity, but furosemide antagonized GABAR currents with low affinity. The neurosteroids alphaxalone and pregnenolone sulfate appropriately modulated GABAR currents. Zinc blocked GABAR currents with low affinity, but lanthanum did not significantly alter NT2-N GABAR currents. Reverse transcription PCR (RT-PCR) performed on RNA from NT2-N cells clearly detected transcripts encoding human 2, 3, 5, 3, 3, and  subtypes. The combined pharmacological and RT-PCR results are most consistent with a single or predominant GABAR isoform composed of an 2 and/or 3 subtype combined with the 3 and 3 subtypes. The data do not rule out receptors containing combinations of 2 and/or 3 subtypes with the 5 subtype or receptors with both 1 and 3 subtypes. The presence or absence or the  subunit in functionally expressed receptors could not be determined.

Key words: GABA; electrophysiology; patch clamp; Ntera2; barbiturate; benzodiazepine; neurosteroid; single channel

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18134993-15$05.00/0

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