Omega-agatoxins differentially block calcium channels in locust, chick and rat synaptosomes.
Three toxins (omega-Agatoxins IA, IIA and IIIA) isolated from the venom of the funnel web spider, Agelenopsis aperta, differentially block depolarization-induced calcium influx in chick, rat and locust synaptosomes. In chick, this block of calcium influx is observed with omega-Agatoxins IIA and IIIA but not with omega-Agatoxin IA. Block by omega-Agatoxin IIA and IIIA is maximal at 70 and 82% respectively of the total depolarization-induced calcium influx; maximal suppression of calcium influx by omega-Conotoxin GVIA (omega-CgTx) is 100%. The IC50 for block with omega-Agatoxin IIA is ca 3 nM as compared with an IC50 of 38 nM for omega-CgTx. Incomplete block of calcium influx at saturating concentrations of omega-Agatoxins IIA and IIIA (above 100 nM) suggests that both omega-Agatoxin-sensitive and -insensitive calcium channels occur in chick brain synaptosomes. In rat cerebrocortical synaptosomes, omega-Agatoxins IA and IIA are only partially effective at blocking depolarization-induced calcium influx, as is omega-CgTx, whilst IIIA blocks 47% of this effective at blocking depolarization-induced calcium influx, as is omega-CgTx, whilst IIIA blocks 47% of this influx. In synaptosomes prepared from the CNS of adult locusts, omega-Agatoxins IA and IIA are most effective at blocking depolarization-induced calcium influx; omega-CgTx and omega-Agatoxin IIIA are ineffective. Block of depolarization-induced calcium influx in chick brain synaptosomes by omega-Agatoxins IIA, IIIA and omega-CgTx suggests that the spider toxin interacts directly with the voltage-dependent calcium channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Pocock
J M
JM
Department of Entomology, University of California, Riverside 92521.
Venema
V J
VJ
Adams
M E
ME
D060848:Agatoxins; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002645:Chickens; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006110:Grasshoppers; D007700:Kinetics; D008297:Male; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D060848:Agatoxins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013111:Spider Venoms; C072527:omega-agatoxin II; D002104:Cadmium; C060465:omega-agatoxin I; C070132:omega-agatoxin III; D003035:Cobalt; D009532:Nickel; D009543:Nifedipine; D011188:Potassium; D002118:Calcium