Relative densities of synaptic and extrasynaptic GABAA receptors on cerebellar granule cells as determined by a quantitative immunogold method

Ion channels gated by the inhibitory neurotransmitter gamma- aminobutyric acid (GABA) are thought to be located in synaptic junctions, but they have also been found throughout the somatodendritic membrane of neurons independent of synapses. To test whether synaptic junctions are enriched in GABAA receptors, and to determine the relative densities of synaptic and extrasynaptic receptors, the alpha 1 and beta 2/3 subunits of the GABAA receptor were localized on cerebellar granule cells using a postembedding immunogold method in cats. Immunoparticle density for the alpha 1 and beta 2/3 subunits was approximately 230 and 180 times more concentrated, respectively, in the synaptic junction made by GABAergic Golgi cell terminals with granule cell dendrites than on the extrasynaptic somatic membrane. Quantification of immunoreactivity revealed one synapse population for the beta 2/3, but appeared to show two populations for the alpha 1 subunit immunoreactivity. The concentration of these subunits on somatic membrane was significantly lower than on the extrasynaptic dendritic membrane. Synaptic junctions with glutamatergic mossy fiber terminals were immunonegative. The results demonstrate that granule cells receiving GABAergic synapses at a restricted location on their distal dendrites exhibit a highly compartmentalized distribution of GABAA receptor in their plasma membrane.