Calcium channel agonists and antagonists modulate voltage dependent calcium influx and neurotransmitter release in the central nervous system

Sites for 3H-dihydropyridines were shown in membranes obtained from cerebellar granule cells in culture. These sites were found to be functional as nitrendipine inhibited the voltage dependent calcium influx in the intact cell while the calcium channel agonist Bay K 8644 increased it. Moreover calcium channel antagonists belonging to different classes were able to reduce voltage dependent calcium influx in a synaptoneurosome preparation from various brain regions. In particular cerebellum, among the different tissues tested, was the area where the calcium channel antagonists were more potent. The effect of calcium channel agonists and antagonists was studied in vivo by nifedipine directly applied by transcerebral dialysis in freely moving rats. Nitrendipine and nifedipine directly applied by dialysis perfusion reduced the K+ stimulated release of dopamine, while in similare experimental condition the calcium agonist Bay K 8644 produced an increase of K+ stimulated dopamine release in the caudate.