Role of Na+/Ca2+ exchange in regulation of neuronal Ca2+ homeostasis requires re-evaluation.
In cultured rat cerebellar granule cells an inhibition of plasma membrane Na+/Ca2+ exchange by removal of external Na+ (replacement with NMDG) caused an increase in [Ca2+]i at rest and a considerable delay in [Ca2+]i recovery from Glu-imposed [Ca2+]i load. These effects did not result from Ca2+ influx through reversed Na+/Ca2+ exchange since they were readily abolished or prevented by using the NMDA receptor inhibitor AP-5 (100 microM) or the NMDA channel blocker memantine (25-50 microM). The effect of Na+/NMDG replacement could be enhanced by: (1) an increase in cytoplasmic Na+ concentration by monensin pretreatment of neurons; (2) external alkalinity, pH 8.5; (3) blockade of the mitochondrial Ca2+ uptake with antimycin plus oligomycin. Analysis of the data obtained led us to conclude that all the changes in [Ca2+]i caused by Na+/NMDG replacement are mainly due to a release of endogenous Glu (reversed Glu uptake) and a subsequent Ca2+ influx through NMDA receptor-mediated channels.
Institute of Pediatrics, Russian Academy of Medical Sciences, Moscow.
T
T
Storozhevykh
N
N
Grigortsevich
E
E
Sorokina
N
N
Vinskaya
O
O
Vergun
V
V
Pinelis
B
B
Khodorov
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008536:Meglumine / Q000494:pharmacology; D008559:Memantine / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D019831:Sodium-Calcium Exchanger; D018698:Glutamic Acid; D008536:Meglumine; D015763:2-Amino-5-phosphonovalerate; D012964:Sodium; D002118:Calcium; D008559:Memantine