Inwardly rectifying potassium (Kir) channels in Mü ller glia play a critical role in the spatial buffering of potassium ions that accumulate during retinal activity. To this end, Kir channels show a polarized subcellular distribution with the predominant channel subunit in Mü ller glia, Kir4.1, clustered in the endfeet of these cells at the inner limiting membrane. However, the molecular mechanisms underlying their distribution have yet to be identified. Here, we show that laminin, agrin and a-dystroglycan (DG) codistribute with Kir4.1 at the inner limiting membrane in the retina and that laminin-1 induces the clustering of a-DG, syntrophin and Kir4.1 in Mü ller cell cultures. In addition, we found that a-DG clusters were enriched for agrin and sought to investigate the role of agrin in their formation using recombinant C-agrins. Both C-agrin 4,8 and C-agrin 0,0 failed to induce a-DG clustering and neither of them potentiated the a-DG clustering induced by laminin-1. Finally, our data reveal that deletion of the PDZ-ligand domain of Kir4.1 prevents their laminin-induced clustering. These findings indicate that both laminin-1 and a-DG are involved in the distribution of Kir4.1 to specific Mü ller cell membrane domains and that this process occurs via a PDZ-domain-mediated interaction. Thus, in the basal lamina laminin is an essential regulator involved in clearing excess potassium released during neuronal activity, thereby contributing to the maintenance of normal synaptic transmission in the retina.
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