Selective clustering of GABA(A) and glycine receptors in the mammalian retina.

ABSTRACT

Molecular cloning has revealed a multiplicity of neurotransmitter receptor isoforms with different subunit compositions. Additionally, there is growing evidence that such receptors are clustered at postsynaptic sites of neurons. Thus, the questions arise whether individual neurons express different receptor isoforms and, if so, whether different isoforms are present within the same cluster or are aggregated at distinct postsynaptic sites. We have studied with immunofluorescence methods and antibodies that recognize specific subunits the distribution of glycine and GABA(A) receptors in mammalian retinae. Alpha ganglion cells were injected in rat or rabbit retinae with a fluorescent marker and then immunostained for receptor localization. Clusters of glycine receptors and clusters of the alpha1, and alpha2, alpha3, and gamma2 subunits of the GABA(A) receptor were found on the somatodendritic membranes of Alpha ganglion cells. Double-immunofluorescence experiments with different combinations of the subunit-specific antibodies showed that the alpha1, alpha2, and alpha3 subunits of the GABA(A) receptor are not colocalized within the same clusters. These results indicate that an individual neuron can express several isoforms of the GABA(A) receptor and that these different isoforms are aggregated at distinct postsynaptic sites. This suggests individual sorting mechanisms of GABAa receptors at GABAergic synapses.