Effect of calcium agonists and antagonists on cerebellar granule cells

In cerebellar cultures, comprising predominantly granule neurones, dihydropyridine (DHP) Ca2+ agonists were potent stimulators of voltage-sensitive 45Ca2+ uptake. Their effect was maximal in partially depolarized cells; at 15 mM K+e half maximal stimulation occurred at about 5 X 10(-8) M BAY K 8644 and 10(-7) M (+)-(S)-202791. Organic Ca2+ antagonists were effective inhibitors of voltage-sensitive calcium entry into granule cells: the order of potency in blocking uptake induced by sub-maximal concentration of K+ and BAY K 8644 was nifedipine greater than (-)-202791 greater than D600. BAY K 8644 also stimulated the release of glutamate, the transmitter of the granule cells, from depolarized cells. Granule cells are therefore a class of neurones whose responsiveness to organic Ca2+ effectors is similar to that of cardiac and smooth muscle. The discrepant findings on the effect of calcium effectors in various preparations of nervous tissues may thus reflect a differential distribution of voltage-sensitive Ca2+ channels in different neuronal cell types.