Jpn. J. Pharmacol. 76 (1), 87-95 (1998)

Protection Against Glutamate Neurotoxicity in Retinal Cultures by Acidic Conditions

Tomoya Saitoh (1), Hiromu K. Mishima (1), Keisuke Shoge (1), Kumatoshi Ishihara (2) and Masashi Sasa (2)

Departments of (1) Ophthalmology and (2) Pharmacology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan

Abstract: 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.

Keywords: Acidosis, Glutamate, Neurotoxicity, Patch-clamp, Retinal cell culture

Copyrightę The Japanese Pharmacological Society 1998

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