title: Nonvesicular release of ATP from rat retinal glial (Müller) cells is differentially mediated in response to osmotic stress and glutamate.
abstract: Retinal glial (Müller) cells release ATP upon osmotic stress or activation of metabotropic glutamate receptors. ATP inhibits the osmotic Müller cell swelling by activation of P2Y1 receptors. In the present study, we determined the molecular pathways of the ATP release from Müller cells in slices of the rat retina. Administration of the ATP/ADPase apyrase induced a swelling of Müller cells under hypoosmotic conditions, and prevented the swelling-inhibitory effect of glutamate, suggesting that swelling inhibition is mediated by extracellular ATP. A hypoosmotic swelling of Müller cells was also observed in the presence of a blocker of multidrug resistance channels (MK-571), a CFTR inhibitor (glibenclamide), and connexin hemichannel blockers (18-α-glycyrrhetinic acid, 100 µM carbenoxolone). The swelling-inhibitory effect of glutamate was prevented by MK-571, the connexin hemichannel blockers, and a pannexin-1 hemichannel blocker (5 µM carbenoxolone). The p-glycoprotein blocker verapamil had no effect. As revealed by single-cell RT-PCR, subpopulations of Müller cells expressed mRNAs for pannexin-1 and -2, and connexins 30, 30.3, 32, 43, 45, and 46. The data may suggest that rat Müller cells release ATP by multidrug resistance channels, CFTR, and connexin hemichannels in response to osmotic stress, while glutamate induces a release of ATP via multidrug resistance channels, connexin hemichannels, and pannexin-1.
authors.affiliation: Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Voigt
authors.forename: Antje
authors.initials: A
authors.lastname: Grosche
authors.forename: Stefanie
authors.initials: S
authors.lastname: Vogler
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Margrit
authors.initials: M
authors.lastname: Hollborn
authors.forename: Leon
authors.initials: L
authors.lastname: Kohen
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017302:Annexins / Q000235:genetics; D017630:Connexins / Q000235:genetics; D063928:Ependymoglial Cells / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009997:Osmotic Pressure; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction
chemical_list: D017302:Annexins; D017630:Connexins; D012333:RNA, Messenger; D018698:Glutamic Acid; D000255:Adenosine Triphosphate