Elevation of intracellular ca(2+) concentration induced by hypoxia in retinal ganglion cells.
OBJECTIVE
To analyze the mechanism of hypoxia-induced changes of the intracellular Ca(2+) concentration ([Ca(2+)](i)) in retinal ganglion cells (RGCs).


METHODS
Fluo-3 was applied to the cut edge of the optic nerve of 6-week-old rats. The retina was sliced, and the Ca images were captured. A hypoxic condition was created by superfusing the retinal slice with an oxygen/glucose-deprived solution.


RESULTS
The retrograde staining method filled the RGCs selectively. Fifteen minutes of hypoxic conditions induced an increase in [Ca(2+)](i) in the RGCs (Delta0.13 +/- 0.03, n = 23). Application of 60 microM DL-2-amino-5-phosphonovaleric acid partially blocked the hypoxia-induced [Ca(2+)](i) increase in dendrites (Delta0.03 +/- 0.02, n = 4, P < 0.05) but not in the somata (Delta0.12 +/- 0.02, n = 9). The RGC dendrites showed a further increase in [Ca(2+)](i) after being switched back to an oxygenated solution (Delta0.14 +/- 0.04, n = 4). Neither 6-cyano-7-nitroquinoxaline-2,3-dione disodium, DL: -threo-beta-benzyloxyaspartate, nifedipine, nor bepridil inhibited the hypoxia-induced [Ca(2+)](i) increase. A Ca(2+)-free superfusion prevented the hypoxia-induced [Ca(2+)](i) increase in the somata (Delta0.07 +/- 0.02, n = 5, P < 0.05) but not in the dendrites (Delta0.16 +/- 0.005, n = 4).


CONCLUSIONS
The mechanism of the hypoxia-induced increase in [Ca(2+)](i) differs between somata and dendrites. The N-methyl-D-aspartate channel of dendrites seems to be the main route of Ca(2+) influx.
Sasaki
Tsugihisa
T
Department of Ophthalmology, Kanazawa University School of Medicine, Kanazawa, Ishikawa, Japan. sasatsug@w5.dion.ne.jp
Kaneko
Akimichi
A
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D015764:Bepridil / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D007424:Intracellular Fluid / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D016202:N-Methylaspartate / Q000031:analogs & derivatives / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011042:Poisons / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D011042:Poisons; D026941:Sodium Channel Blockers; D019831:Sodium-Calcium Exchanger; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015764:Bepridil; C056639:2-amino-5-phosphopentanoic acid; C083705:N-methyl-DL-aspartic acid; D014633:Valine; D009543:Nifedipine; D002118:Calcium