Expression and Function of P2Y Receptors on Muller Cells of the Postnatal Rat Retina

In the postnatal and mature retina, many processes are controlled by the action of nucleotides. Their effects are partly mediated via activation of metabotropic P2Y receptors. However, little is known about the developmental regulation and cellular localization of P2Y receptor subtypes. Combining immunohistochemical and neurophysiological methods, we investigated the developmental expression of P2Y receptors on Muller cells, the principal macroglial cells of the retina. The P2Y(1) and the P2Y4 receptors, but no other subtypes, were unequivocally localized on Muller cells. P2Y(1) was expressed from postnatal day 5 (P5) on and mediated a calcium response to ATP in Muller cells as well as a volume regulatory signaling cascade preventing Muller cells from swelling under hypotonic conditions. Differentiation of Muller cells was accompanied by a change of the calcium response pattern; the calcium responses in Muller cell endfeet persisted, but ATP responsiveness of Muller cell somata disappeared. P2Y(4) immunoreactivity was observed in Muller cell endfeet and synaptic terminals of rod bipolar cells from P20 on. Activated protein kinases were detected by immunohistochemistry; p-ERK occurred in Muller cells and amacrine cells, whereas p-Akt was detected in bipolar cells. Our data indicate that purinergic signaling via P2Y(1) and P2Y(4) receptors might contribute to differentiation processes in the postnatal retina. (C) 2009 Wiley-Liss, Inc.