Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas
| Autor: | Andrew Palma, Katalin Tarczy-Hornoch, Balazs G. Szoke, Cong Ruth, James A. Miller, Gang Wang, David J. Dooley, Joseph A. Loo, George P. Miljanich, Robert Newcomb, Laszlo Urge, Xiao-hua Chen, William F. Hopkins, Richard W. Tsien, Laszlo Nadasdi, José R. Lemos |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Patch-Clamp Techniques Xenopus Molecular Sequence Data Spider Venoms Venom Peptide Transfection Biochemistry Cell Line Rats Sprague-Dawley Potassium Channel Blockers Tumor Cells Cultured Animals Humans Amino Acid Sequence Hysterocrates gigas Tarantula chemistry.chemical_classification biology Calcium channel Antagonist biology.organism_classification Calcium Channel Blockers Rats chemistry Oocytes Ligand-gated ion channel Calcium Channels SNX-482 Peptides Sodium Channel Blockers |
| Zdroj: | Biochemistry. 37(44) |
| ISSN: | 0006-2960 |
| Popis: | We describe the first potent and selective blocker of the class E Ca2+channel. SNX-482, a novel 41 amino acid peptide present in the venom of the African tarantula, Hysterocrates gigas, was identified through its ability to inhibit human class E Ca2+ channels stably expressed in a mammalian cell line. An IC50 of 15-30 nM was obtained for block of the class E Ca2+ channel, using either patch clamp electrophysiology or K+-evoked Ca2+ flux. At low nanomolar concentrations, SNX-482 also blocked a native resistant or R-type Ca2+ current in rat neurohypophyseal nerve terminals, but concentrations of 200-500 nM had no effect on R-type Ca2+ currents in several types of rat central neurons. The peptide has the sequence GVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OH and is homologous to the spider peptides grammatoxin S1A and hanatoxin, both peptides with very different ion channel blocking selectivities. No effect of SNX-482 was observed on the following ion channel activities: Na+ or K+ currents in several cultured cell types (up to 500 nM); K+ current through cloned potassium channels Kv1.1 and Kv1. 4 expressed in Xenopus oocytes (up to 140 nM); Ca2+ flux through L- and T-type Ca2+ channels in an anterior pituitary cell line (GH3, up to 500 nM); and Ba2+ current through class A Ca2+ channels expressed in Xenopus oocytes (up to 280 nM). A weak effect was noted on Ca2+ current through cloned and stably expressed class B Ca2+ channels (IC50500 nM). The unique selectivity of SNX-482 suggests its usefulness in studying the diversity, function, and pharmacology of class E and/or R-type Ca2+ channels. |
| Databáze: | OpenAIRE |
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