Abstract
Venon of the funnel web spider Agelenopsis aperta was fractionated and screened for activity against the mammalian presynaptic, voltage-dependent Ca 2+ channel coupled to glutamate exocytosis. A purified toxin (Aga-GI) from this venom inhibits glutamate exocytosis evoked by elevated potassium or by 4-aminopyridine but is without effect on ionomycin-evoked release. At the same time a partial inhibition of the depolarisation-evoked elevation of cytoplasmic free Ca 2+ is seen. The toxin does not inhibit 4-aminopyridine- or potassium-evoked depolarisation, or block Ca 2+-dependent, potassium-evoked [ 3H]noradrenaline release. The results indicate that the venom contains a toxin capable of inhibiting the presynaptic voltage-dependent Ca 2+ channel coupled to glutamate exocytosis in the mammalian central nervous system. This channel is resistant to block by either ω-conotoxin GVIA or nifedipine. Thus Aga-GI is a novel tool with which to probe this elusive neuronal calcium channel.
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