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J Gen Physiol. Jan 1, 1989; 93(1): 67–83.
PMCID: PMC2216202

Modification of Na channel gating by an alpha scorpion toxin from Tityus serrulatus

Abstract

The effects of TsIV-5, a toxin isolated from the Brazilian scorpion Tityus serrulatus, on whole-cell and single-channel Na currents were determined in N18 neuroblastoma cells. In whole-cell records at a test potential of -10 mV, external application of 500 nM TsIV-5 slowed inactivation 20-fold and increased peak current by about one-third without changing time-to-peak. Both the steady-state activation and inactivation curves were shifted to more negative potentials. Other alpha scorpion toxins produce similar effects but the single-channel mechanism is not known. TsIV-5 caused a voltage-dependent prolongation of mean single-channel open time such that at a test potential of -60 mV no change was observed, whereas at -20 mV mean open time increased about threefold and prolonged bursting was observed. Macroscopic current reconstructed from summed single-channel records showed a characteristic toxin-induced potentiation of peak current and a 20-fold slowing of the decay phase. TsIV-5 does not discriminate between tissue- specific Na channel subtypes. Prolonged open times and bursting were also observed in toxin-treated Na channels from rat ventricular myocytes, rat cortical neurons, and mouse skeletal muscle. The toxin effects are shown to be consistent with a kinetic model in which TsIV-5 selectively interferes with the ability of the channel to reach the inactivated state.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aldrich RW, Corey DP, Stevens CF. A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature. 1983 Dec 1;306(5942):436–441. [PubMed]
  • Barhanin J, Giglio JR, Léopold P, Schmid A, Sampaio SV, Lazdunski M. Tityus serrulatus venom contains two classes of toxins. Tityus gamma toxin is a new tool with a very high affinity for studying the Na+ channel. J Biol Chem. 1982 Nov 10;257(21):12553–12558. [PubMed]
  • Colquhoun D, Sakmann B. Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate. J Physiol. 1985 Dec;369:501–557. [PMC free article] [PubMed]
  • Couraud F, Jover E, Dubois JM, Rochat H. Two types of scorpion receptor sites, one related to the activation, the other to the inactivation of the action potential sodium channel. Toxicon. 1982;20(1):9–16. [PubMed]
  • Cruz LJ, Gray WR, Olivera BM, Zeikus RD, Kerr L, Yoshikami D, Moczydlowski E. Conus geographus toxins that discriminate between neuronal and muscle sodium channels. J Biol Chem. 1985 Aug 5;260(16):9280–9288. [PubMed]
  • Fenwick EM, Marty A, Neher E. Sodium and calcium channels in bovine chromaffin cells. J Physiol. 1982 Oct;331:599–635. [PMC free article] [PubMed]
  • Fox JM. Ultra-slow inactivation of the ionic currents through the membrane of myelinated nerve. Biochim Biophys Acta. 1976 Mar 5;426(2):232–244. [PubMed]
  • Gomez MV, Diniz CR. Separation of toxic components from the brazillian scorpion Tityus serrulatus venom. Mem Inst Butantan. 1966;33(3):899–902. [PubMed]
  • Gonoi T, Hille B. Gating of Na channels. Inactivation modifiers discriminate among models. J Gen Physiol. 1987 Feb;89(2):253–274. [PMC free article] [PubMed]
  • Gonoi T, Hille B, Catterall WA. Voltage clamp analysis of sodium channels in normal and scorpion toxin-resistant neuroblastoma cells. J Neurosci. 1984 Nov;4(11):2836–2842. [PubMed]
  • Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. [PubMed]
  • HODGKIN AL, HUXLEY AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. [PMC free article] [PubMed]
  • Lux HD, Brown AM. Patch and whole cell calcium currents recorded simultaneously in snail neurons. J Gen Physiol. 1984 May;83(5):727–750. [PMC free article] [PubMed]
  • Nagy K. Evidence for multiple open states of sodium channels in neuroblastoma cells. J Membr Biol. 1987;96(3):251–262. [PubMed]
  • Patlak J, Horn R. Effect of N-bromoacetamide on single sodium channel currents in excised membrane patches. J Gen Physiol. 1982 Mar;79(3):333–351. [PMC free article] [PubMed]
  • Possani LD, Martin BM, Svendsen I, Rode GS, Erickson BW. Scorpion toxins from Centruroides noxius and Tityus serrulatus. Primary structures and sequence comparison by metric analysis. Biochem J. 1985 Aug 1;229(3):739–750. [PMC free article] [PubMed]
  • Quandt FN. Burst kinetics of sodium channels which lack fast inactivation in mouse neuroblastoma cells. J Physiol. 1987 Nov;392:563–585. [PMC free article] [PubMed]
  • Renaud JF, Fosset M, Schweitz H, Lazdunski M. The interaction of polypeptide neurotoxins with tetrodotoxin-resistant Na+ channels in mammalian cardiac cells. Correlation with inotropic and arrhythmic effects. Eur J Pharmacol. 1986 Jan 21;120(2):161–170. [PubMed]
  • Strichartz G, Rando T, Wang GK. An integrated view of the molecular toxinology of sodium channel gating in excitable cells. Annu Rev Neurosci. 1987;10:237–267. [PubMed]
  • Strichartz GR, Wang GK. Rapid voltage-dependent dissociation of scorpion alpha-toxins coupled to Na channel inactivation in amphibian myelinated nerves. J Gen Physiol. 1986 Sep;88(3):413–435. [PMC free article] [PubMed]
  • Vandenberg CA, Horn R. Inactivation viewed through single sodium channels. J Gen Physiol. 1984 Oct;84(4):535–564. [PMC free article] [PubMed]
  • Vijverberg HP, Pauron D, Lazdunski M. The effect of Tityus serrulatus scorpion toxin gamma on Na channels in neuroblastoma cells. Pflugers Arch. 1984 Jul;401(3):297–303. [PubMed]
  • Wheeler KP, Watt DD, Lazdunski M. Classification of Na channel receptors specific for various scorpion toxins. Pflugers Arch. 1983 Apr;397(2):164–165. [PubMed]
  • Yatani A, Kirsch GE, Possani LD, Brown AM. Effects of New World scorpion toxins on single-channel and whole cell cardiac sodium currents. Am J Physiol. 1988 Mar;254(3 Pt 2):H443–H451. [PubMed]

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