P2X(7) receptors in Muller glial cells from the human retina

ATP has been shown to be an important extracellular signaling molecule. The re are two subgroups of receptors for ATP (and other purines and pyrimidine s): the ionotropic P2X and the G-protein-coupled P2Y receptors. Different s ubtypes of these receptors have been identified by molecular biology, but l ittle is known about their functional properties in the nervous system. Her e we present data for the existence of P2 receptors in Muller (glial) cells of the human retina. The cells were studied by immunocytochemistry, electr ophysiology, Ca2+-microfluorimetry, and molecular biology. They displayed b oth P2Y and P2X receptors. Freshly enzymatically isolated cells were used t hroughout the study. Although the [Ca2+](i) response to ATP was dominated b y release from intracellular stores, there is multiple evidence that the AT P-induced membrane currents were caused by an activation of P2X(7) receptor s. Immunocytochemistry and single-cell RT-PCR revealed the expression of P2 X7 receptors by Muller cells. In patch-clamp studies, we found that (1) ben zoyl-benzoyl ATP (BzATP) was the most effective agonist to evoke large inwa rd currents and (2) the currents were abolished by P2X antagonists; however , (3) long-lasting application of BzATP did not cause an opening of large p ores in addition to the cationic channels. By microfluorimetry it was shown that the P2X receptors mediated a Ca2+ influx that contributed a small com ponent to the total [Ca2+](i) response. Activation of P2X receptors may mod ulate the uptake of neurotransmitters from the extracellular space by Mulle r cells in the retina.