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ORIGINAL ARTICLE

Cultured Hippocampal Pyramidal Neurons Express Two Kinds of GABA_A Receptors

Department of Neurology, University of Virginia, School of Medicine, Charlottesville, Virginia, (P.S.M, C.S., H.P.G., J.K.); University of Virginia, School of Medicine, Charlottesville, Virginia (M.C.); Brain Research Institute of the Medical University Vienna, Division of Biochemistry, and Molecular Biology, Vienna, Austria (W.S.)

Abstract

We combined a study of the subcellular distribution of the 1, 2, 4, 1, 2/3, 2, and subunits of the GABA_A receptor with an electrophysiological analysis of GABA_A receptor currents determine the to types of receptors expressed on cultured hippocampal pyramidal neurons. The immunocytochemistry study demonstrated that 1, 2, 2/3, and 2 subunits formed distinct clusters of various sizes, which were colocalized with clusters of glutamate decarboxylase (GAD) immunoreactivity at rates ranging from 22 to 58%. In contrast, 4, 1, and subunits were distributed diffusely over the cell soma and neuronal processes of cultured neurons and did not colocalize with the synaptic marker GAD. Whole-cell GABA receptor currents were moderately sensitive to GABA_A and were modulated by diazepam. The whole-cell currents were also enhanced by the neurosteroid allopregnanolone (10 nM). Tonic currents, measured as changes in baseline current and noise, were sensitive to Zn²⁺, furosemide, and loreclezole; they were insensitive to diazepam. These studies suggest that two kinds of GABA_A receptors are expressed on cultured hippocampal neurons. One kind of receptor formed clusters, which were present at GABAergic synapses and in the extrasynaptic membrane. The 1, 2, 2/3, and 2 subunits were contained in clustered receptors. The second kind was distributed diffusely in the extrasynaptic membrane. The 4, 1, and subunits were contained in these diffusely distributed receptors. The properties of tonic currents recorded from these neurons were similar to those from recombinant receptors containing 4, 1, and subunits.

Address correspondence to: Dr. Jaideep Kapur, Department of Neurology, Box 800394, University of Virginia-HSC, Charlottesville, VA. E-mail: jk8t{at}virginia.edu

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