THE CALCIUM-CHANNEL COUPLED TO THE EXOCYTOSIS OF L-GLUTAMATE FROM CEREBELLAR GRANULE CELLS IS INHIBITED BY THE SPIDER TOXIN, AGA-GI

The increase in cytosolic calcium, [Ca2+]c, evoked with 50 mM KCl in c erebellar granule cells consists of four components; (1) a rapidly ina ctivating transient or spike; (2) a nifedipine-sensitive non-inactivat ing plateau; (3) an Aga-GI (spider toxin) sensitive non-inactivating p lateau; (4) a residual non-inactivating plateau insensitive to nifedip ine and Aga-GI. None of these components is blocked by synthetic argin ine polyamine toxin, spermine, (+)-MK-801 hydrogen maleate, D(-)-2-ami no-5-phosphonopentanoic acid or omega-conotoxin-GVIA. The proposed P-t ype channel antagonist, omega-agatoxin-IVA, has a limited but non-sign ificant effect on the elevated plateau [Ca2+]c. L-type Ca2+ channels a re localized primarily on the soma whereas the component of the platea u which is blocked specifically by Aga-GI is localized primarily on th e cell neurites. The latter component is coupled to the exocytosis of endogenous glutamate evoked with 50 mM KCl.