RELATIVE DENSITIES OF SYNAPTIC AND EXTRASYNAPTIC GABA(A) RECEPTORS ONCEREBELLAR GRANULE CELLS AS DETERMINED BY A QUANTITATIVE IMMUNOGOLD METHOD

Ion channels gated by the inhibitory neurotransmitter gamma-aminobutyr ic acid (GABA) are thought to be located in synaptic junctions, but th ey have also been found throughout the somatodendritic membrane of neu rons independent of synapses. To test whether synaptic junctions are e nriched in GABA(A) receptors, and to determine the relative densities of synaptic and extrasynaptic receptors, the alpha 1 and beta 2/3 subu nits of the GABA(A) receptor were localized on cerebellar granule cell s using a postembedding immunogold method in cats. Immunoparticle dens ity for the alpha 1 and beta 2/3 subunits was approximately 230 and 18 0 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 immunoreactivit y revealed one synapse population for the beta 2/3, but appeared to sh ow two populations for the alpha 1 subunit immunoreactivity. The conce ntration of these subunits on somatic membrane was significantly lower than on the extrasynaptic dendritic membrane. Synaptic junctions with glutamatergic messy fiber terminals were immunonegative. The results demonstrate that granule cells receiving GABAergic synapses at a restr icted location on their distal dendrites exhibit a highly compartmenta lized distribution of GABA(A) receptor in their plasma membrane.