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 × 10⁻⁸ M BAY K 8644 and 10⁻⁷ M(+)-(S)-202 791. 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 > (−)-202 791 > 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.