Effect of magnesium on calcium influx activated by glutamate and its agonists in cultured cerebellar granule cells.
The effects of Mg2+ on the glutamate-, kainate-, N-methyl-D-aspartate- and quisqualate-induced influx of 45Ca2+ were studied in cultured cerebellar granule cells. The N-methyl-D-aspartate- and quisqualate-evoked influx was totally and the kainate- and glutamate-evoked influx partially blocked in 1.3 mM extracellular Mg2+. The increase in influx induced by kainate, quisqualate and glutamate was maximal at 0.1 mM Mg2+, whereas N-methyl-D-aspartate was most effective in totally Mg(2+)-free media. D-2-Amino-5-phosphonovalerate blocked partially and phencyclidine completely the enhancement of Ca2+ influx by 1 mM quisqualate in 0.1-mM Mg2+ medium. The effect of 10 microM quisqualate was also significantly inhibited by antagonists specific for different glutamate receptor subtypes, including N-methyl-D-aspartate, (RS) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and metabotropic receptors. This evidences a heterogeneous action of quisqualate, mediated by different glutamate receptor subtypes in 0.1 mM Mg2+ medium. The efficacy of quisqualate in inducing influx of Ca2+ and the selectivity of antagonists for different receptors are also modified by extracellular Mg2+.
Department of Biomedical Sciences, University of Tampere, Finland.
V
V
Varga
R
R
Janáky
I
I
Holopainen
P
P
Saransaari
S S
SS
Oja
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
D002132:Calcium Radioisotopes; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D014700:Verapamil; D008274:Magnesium; D009543:Nifedipine; D010622:Phencyclidine; D007608:Kainic Acid; D002118:Calcium