A toxin (Aga-GI) from the venom of the spider Agelenopsis aperta inhibits the mammalian presynaptic Ca2+ channel coupled to glutamate exocytosis.
Venom of the funnel web spider Agelenopsis aperta was fractionated and screened for activity against the mammalian presynaptic, voltage-dependent Ca2+ 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 Ca2+ 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 Ca2+ channel coupled to glutamate exocytosis in the mammalian central nervous system. This channel is resistant to block by either omega-conotoxin GVIA or nifedipine. Thus Aga-GI is a novel tool with which to probe this elusive neuronal calcium channel.
Department of Biochemistry, University of Dundee, Scotland, UK.
J M
JM
Pocock
D G
DG
Nicholls
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005591:Chemical Fractionation; D005089:Exocytosis; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D013111:Spider Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D020866:omega-Conotoxin GVIA
C077471:Aga-GI toxin; D015220:Calcium Channels; D005971:Glutamates; D010456:Peptides, Cyclic; D013111:Spider Venoms; D018698:Glutamic Acid; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine