Inhibition of neuronal Ca2+ channel currents by the funnel web spider toxin omega-Aga-IA.
Ca2+ channel currents were recorded from cultured rat dorsal root ganglion neurons and cerebellar granule cells using the whole-cell recording variant of the patch clamp technique. omega-Aga-IA, a toxin purified from the venom of the American funnel web spider, Agelenopsis aperta, markedly inhibited high threshold barium currents (lBa) when applied at 10 nM concentration. The low threshold T-type current activated at Vc = -30 mV and the outward (Ca2+ channel) current activated at +120 mV were significantly less sensitive to omega-Aga-IA, omega-Conotoxin GVIA (1 microM) inhibited IBa irreversibly. In contrast, the action of omega-Aga-IA was partially reversed 5 min after its removal. The voltage-activated calcium current (ICa) was inhibited by omega-Aga-IA in a manner different from IBa. ICa measured at the end of a 100-msec voltage step command was reduced to a greater extent than the peak current. The residual ICa following application of omega-Aga-IA was a fast transient current. omega-Aga-IA did not inhibit voltage-activated sodium currents from dorsal root ganglion neurons in the absence of tetrodotoxin. omega-Aga-IA abolished the dihydropyridine (+)-202-791-sensitive L-type current component of IBa. We conclude that omega-Aga-IA is a very potent inhibitor of neuronal voltage-activated Ca2+ channel currents and that it may prove to be a useful tool in the characterization and isolation of Ca2+ channels.
Scott
R H
RH
Department of Physiology, St. George's Hospital Medical School, London, United Kingdom.
Dolphin
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Bindokas
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Adams
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D060848:Agatoxins; D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004553:Electric Conductivity; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology; 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; C060465:omega-agatoxin I; D001464:Barium; D020866:omega-Conotoxin GVIA