Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas

Biochemistry. 1998 Nov 3;37(44):15353-62. doi: 10.1021/bi981255g.


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 (IC50 > 500 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium Channel Blockers / chemistry*
  • Calcium Channel Blockers / isolation & purification
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / physiology
  • Cell Line
  • Humans
  • Male
  • Molecular Sequence Data
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Peptides / chemistry*
  • Peptides / isolation & purification
  • Peptides / physiology
  • Potassium Channel Blockers
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channel Blockers
  • Spider Venoms / chemistry*
  • Spider Venoms / isolation & purification
  • Spider Venoms / pharmacology
  • Transfection
  • Tumor Cells, Cultured
  • Xenopus


  • Calcium Channel Blockers
  • Calcium Channels
  • Peptides
  • Potassium Channel Blockers
  • SNX 482
  • Sodium Channel Blockers
  • Spider Venoms