Inhibition of N- and L-type Ca2+ channels by the spider venom toxin omega-Aga-IIIA.
omega-Aga-IIIA, an 8.5-kDa peptide toxin isolated from the venom of Agelenopsis aperta, was found to be a highly potent inhibitor of Ca channels in cardiac muscle and in peripheral and central neurons of rats and frogs. Cardiac L-type Ca channels were completely (Kd approximately 0.6 nM) blocked by omega-Aga-IIIA. In sensory neurons, the toxin inhibited most high-threshold Ca current but not T-type Ca current. omega-Aga-IIIA blocked with similar potency (Kd approximately 1.5 nM) both omega-conotoxin GVIA-sensitive and dihydropyridine-sensitive current components but left a fraction (approximately 35%) of high-threshold current that was also resistant to omega-conotoxin and dihydropyridines. The toxin blocks N- and L-type channels with equal potency and therefore may identify a high-affinity binding site common to these two Ca channel types.
Mintz
I M
IM
Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
Venema
V J
VJ
Adams
M E
ME
Bean
B P
BP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D060848:Agatoxins; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D009132:Muscles / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011892:Rana catesbeiana; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology*; D020866:omega-Conotoxin GVIA
D060848:Agatoxins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010456:Peptides, Cyclic; D013111:Spider Venoms; C070132:omega-agatoxin III; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA