SWELLING OF MULLER CELLS INDUCED BY AP3 AND GLUTAMATE TRANSPORT SUBSTRATES IN RAT RETINA

Previous studies have shown that a single systemic injection of 2-amin o-3-phosphonopropionate (AP3), an agonist/antagonist at metabotropic g lutamate receptors, produces marked swelling of rodent Muller cells. T o investigate the effects of AP3 on Muller cells, we used in vitro ret inal segments prepared from 30 day old rats. Incubation with AP3 for 1 h or more caused severe swelling of Muller cells with the appearance of mitotic cellular profiles in the outer nuclear layer. The Muller ce ll swelling was mimicked by substrates for glutamate transporters, sug gesting that AP3 may produce its effects via transport into glial cell s. To determine whether AP3 is a substrate for glutamate transporters, we studied cultured rat hippocampal astrocytes using whole-cell patch clamp recordings. In hippocampal astrocytes, AP3 activated currents v ia an Naf-dependent glutamate transporter. Consistent with this, subst itution of extracellular sodium with choline blocked Muller cell swell ing in the rat retina. These results indicate that the acute glial swe lling produced by AP3 results primarily from a fluid shift that accomp anies the transport of AP3 and sodium into Muller cells (C) 1996 Wiley -Liss, Inc.