Kainate elicits elevated nuclear calcium signals in retinal neurons via calcium-induced calcium release.
Intracellular Ca2+ was imaged in cultured neonatal rat retinal neurons using the Ca(2+)-sensitive dye fluo-3 and confocal scanning laser microscopy. Depolarization via elevation of bath K+ concentration resulted in large cytoplasmic and nuclear Ca2+ signals; responses in the nucleus exceeded those of the cytoplasm. Glutamate or kainate application elicited the same intracellular pattern of elevated Ca2+ signals. Kainate stimulation was blocked by the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and greatly reduced by removing Ca2+ from the bath and adding ethylene glycol-bis (beta-amino-ethyl ether) N,N,N',N'-tetraacetic acid (EGTA). Kainate was equally effective in eliciting Ca2+ signals when bath Na+ was replaced with equimolar concentrations of choline, or in the presence of the NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV). Caffeine treatment significantly reduced the kainate-induced intracellular Ca2+ response. These results suggest that Ca2+ can enter through the kainate receptor of retinal neurons and amplify the Ca2+ signals in the cytoplasm and nucleus by releasing Ca2+ from intracellular stores.
Kocsis
J D
JD
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.
Rand
M N
MN
Chen
B
B
Waxman
S G
SG
Pourcho
R
R
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D007608:Kainic Acid / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D012964:Sodium / Q000494:pharmacology
D011810:Quinoxalines; D002110:Caffeine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D012964:Sodium; D007608:Kainic Acid; D002118:Calcium