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The effects of Mg on the glutamate-, kainate-, N-methyl- d-aspartate- and quisqualate-induced influx ofCa 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 Mg. The increase in influx induced by kainate, quisqualate and glutamate was maximal at 0.1 mM Mg, whereas N-methyl- d-aspartate was most effective in totally Mg-free media. d-2-Amino-5-phosphonovalerate blocked partially and phencyclidine completely the enhancement of Ca influx by 1 mM quisqualate in 0.1-mM Mg medium. The effect of 10 μM quisqualate was also significantly inhibited by antagonists specific for different glutamate receptor subtypes, including N-methyl- d-aspartate, (RS)α-amino-3-hydroxy-5-methyl-4-isozazolepropionate and metabotropic recptors. This evidences a heterogeneous action of quisqualate, mediated by different glutamate receptor subtypes in 0.1 mM Mg medium. The efficacy of quisqualate in inducing influx of Ca and the selectivity of antagonists for different receptors are also modified by extracellular Mg. [ABSTRACT FROM AUTHOR]