Inhibition of a dihydropyridine, omega-conotoxin insensitive Ca2+ channel in rat synaptosomes by venom of the spider Hololena curta.
Inhibition of the N and L type Ca2+ channels with omega conotoxin GVIA (omega-CgTx) together with the dihydropyridine (-)-202-791 produces slight reduction (congruent to 25%) of K(+)-evoked Ca2+ influx in mammalian synaptosomes. These results and others suggest the existence of a third high threshold voltage sensitive calcium channel (VSCC) responsible for the majority of influx. Venom from the funnel web spider Hololena curta potently and persistently inhibited Ca2+ influx in rat cortical synaptosomes (IC50 1:10,000 or 4.21 micrograms/venom protein/ml of synaptosomes). Also Ca2+ influx in cerebellar synaptosomes was inhibited in a similar manner. K(+)-evoked tritium release from synaptosomes labeled with [3H]noradrenaline was inhibited by Hololena venom (congruent to 60% reduction at 10 micrograms/venom protein). Inhibition of Ca2+ influx by venom was unaffected by combined omega-CgTx and (-)-202-791 pretreatment (both 1 microM). Hololena venom and its active constituent should provide useful tools to investigate the role of this novel Ca2+ channel in neuronal function.
Lundy
P M
PM
Defence Research Establishment Suffield, Ralston, Alberta, Canada.
Hong
A
A
Frew
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002645:Chickens; D066298:In Vitro Techniques; D009539:Nicotinic Acids / Q000494:pharmacology*; D010069:Oxadiazoles; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009539:Nicotinic Acids; D010069:Oxadiazoles; D010456:Peptides, Cyclic; D013111:Spider Venoms; C049834:PN 202-791; D020866:omega-Conotoxin GVIA; D002118:Calcium