Protection against glutamate neurotoxicity in retinal cultures by acidic conditions.
We evaluated the effects of extracellular acidic conditions on glutamate-induced death in cultured retinal neurons. Primary retinal cultures, obtained from 3- to 5-day-old Wistar rats, were estimated to be consisted of mainly amacrine cells (90%) together with a small population of horizontal (8%) and ganglion cells (2%). We examined the effects of acidic pH (pH 6.0 to 7.0) on glutamate neurotoxicity by monitoring the delayed death of retinal neurons induced by brief (10 min) exposure to 1 mM glutamate followed by a 24-hr incubation. The glutamate-induced delayed death of cultured retinal neurons was attenuated with an acidic pH between 6.0 and 7.0. Furthermore, whole-cell patch-clamp recordings were taken from retinal neurons to examine the effects of acidic pH on N-methyl-D-aspartate (NMDA) or kainate receptor-mediated currents. NMDA- and kainate-induced currents were suppressed at pH 6.0 to 7.0 and pH 6.0 to 6.5, respectively. The acidity of the medium protected the retinal neurons from glutamate-induced delayed death, probably by inhibiting NMDA and/or kainate receptor activation.
Saitoh
T
T
Department of Ophthalmology, Hiroshima University School of Medicine, Japan.
Mishima
H K
HK
Shoge
K
K
Ishihara
K
K
Sasa
M
M
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000143:Acids; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000143:Acids; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate