Site-3 Toxins and Cardiac Sodium Channels

Overview

Journal Toxicon

Specialty Toxicology

Date 2006 Nov 10

PMID 17092528

Citations 27

Authors

Dorothy A Hanck

Michael F Sheets

Affiliations

Soon will be listed here.

Abstract

Site-3 toxins are small polypeptide venoms from scorpions, sea anemones, and spiders that bind with a high specificity to the extracellular surface of voltage-gated Na channels. After binding to a site near the S4 segment in domain IV the toxin causes disruption of the normal fast inactivation transition resulting in a marked prolongation of the action potentials of excitable tissues including those of cardiac and skeletal muscle and nerve. In this review we discuss the specific binding interactions between residues of the toxin and those of the Na channel, and the specific modification of Na channel kinetic behavior leading to a change in fast inactivation focusing on interactions deduced primarily from the study of sea anemone toxins and the cardiac Na channel (Na(V)1.5). We also illustrate the usefulness of site-3 toxins in the study of altered Na channel behavior by drug-modification.

Citing Articles

Resurgent current in context: Insights from the structure and function of Na and K channels.

Aman T, Raman I Biophys J. 2023; 123(14):1924-1941.

PMID: 38130058 PMC: 11309984. DOI: 10.1016/j.bpj.2023.12.016.

Historical Perspective of the Characterization of Conotoxins Targeting Voltage-Gated Sodium Channels.

Groome J Mar Drugs. 2023; 21(4).

PMID: 37103349 PMC: 10142487. DOI: 10.3390/md21040209.

Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors.

Angsutararux P, Dutta A, Marras M, Abella C, Mellor R, Shi J J Gen Physiol. 2023; 155(5).

PMID: 36944081 PMC: 10038838. DOI: 10.1085/jgp.202213300.

Characterization of the First Animal Toxin Acting as an Antagonist on AT1 Receptor.

Van Baelen A, Iturrioz X, Chaigneau M, Kessler P, Llorens-Cortes C, Servent D Int J Mol Sci. 2023; 24(3).

PMID: 36768653 PMC: 9916866. DOI: 10.3390/ijms24032330.

The Sea Anemone Neurotoxins Modulating Sodium Channels: An Insight at Structure and Functional Activity after Four Decades of Investigation.

Monastyrnaya M, Kalina R, Kozlovskaya E Toxins (Basel). 2023; 15(1).

PMID: 36668828 PMC: 9863223. DOI: 10.3390/toxins15010008.

References

Rando T, Wang G, Strichartz G . The interaction between the activator agents batrachotoxin and veratridine and the gating processes of neuronal sodium channels. Mol Pharmacol. 1986; 29(5):467-77. View

Strichartz G, Wang G . Rapid voltage-dependent dissociation of scorpion alpha-toxins coupled to Na channel inactivation in amphibian myelinated nerves. J Gen Physiol. 1986; 88(3):413-35. PMC: 2228828. DOI: 10.1085/jgp.88.3.413. View

Grant A, Starmer C . Mechanisms of closure of cardiac sodium channels in rabbit ventricular myocytes: single-channel analysis. Circ Res. 1987; 60(6):897-913. DOI: 10.1161/01.res.60.6.897. View

Schreibmayer W, Kazerani H, Tritthart H . A mechanistic interpretation of the action of toxin II from Anemonia sulcata on the cardiac sodium channel. Biochim Biophys Acta. 1987; 901(2):273-82. DOI: 10.1016/0005-2736(87)90124-6. View

Warashina A, Jiang Z, Ogura T . Potential-dependent action of Anemonia sulcata toxins III and IV on sodium channels in crayfish giant axons. Pflugers Arch. 1988; 411(1):88-93. DOI: 10.1007/BF00581651. View

Tejedor F, Catterall W . Site of covalent attachment of alpha-scorpion toxin derivatives in domain I of the sodium channel alpha subunit. Proc Natl Acad Sci U S A. 1988; 85(22):8742-6. PMC: 282537. DOI: 10.1073/pnas.85.22.8742. View

Fletcher J, Chapman B, Mackay J, Howden M, King G . The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel. Structure. 1998; 5(11):1525-35. DOI: 10.1016/s0969-2126(97)00301-8. View

Benzinger G, KYLE J, Blumenthal K, Hanck D . A specific interaction between the cardiac sodium channel and site-3 toxin anthopleurin B. J Biol Chem. 1998; 273(1):80-4. DOI: 10.1074/jbc.273.1.80. View

Little M, Zappia C, Gilles N, Connor M, Tyler M, Martin-Eauclaire M . delta-Atracotoxins from australian funnel-web spiders compete with scorpion alpha-toxin binding but differentially modulate alkaloid toxin activation of voltage-gated sodium channels. J Biol Chem. 1998; 273(42):27076-83. DOI: 10.1074/jbc.273.42.27076. View

10.

Little M, Wilson H, Zappia C, Cestele S, Tyler M, Martin-Eauclaire M . Delta-atracotoxins from Australian funnel-web spiders compete with scorpion alpha-toxin binding on both rat brain and insect sodium channels. FEBS Lett. 1998; 439(3):246-52. DOI: 10.1016/s0014-5793(98)01378-7. View

11.

Sheets M, Hanck D . Gating of skeletal and cardiac muscle sodium channels in mammalian cells. J Physiol. 1998; 514 ( Pt 2):425-36. PMC: 2269069. DOI: 10.1111/j.1469-7793.1999.425ae.x. View

12.

Benzinger G, Tonkovich G, Hanck D . Augmentation of recovery from inactivation by site-3 Na channel toxins. A single-channel and whole-cell study of persistent currents. J Gen Physiol. 1999; 113(2):333-46. PMC: 2223375. DOI: 10.1085/jgp.113.2.333. View

13.

Seibert A, Liu J, Hanck D, Blumenthal K . Role of Asn-16 and Ser-19 in anthopleurin B binding. Implications for the electrostatic nature of Na(V) site 3. Biochemistry. 2004; 43(22):7082-9. DOI: 10.1021/bi0496135. View

14.

Oliveira J, Redaelli E, Zaharenko A, Cassulini R, Konno K, Pimenta D . Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop. J Biol Chem. 2004; 279(32):33323-35. DOI: 10.1074/jbc.M404344200. View

15.

Beress L, Beress R . Purification of three polypeptides with neuro- and cardiotoxic activity from the sea anemone Anemonia sulcata. Toxicon. 1975; 13(5):359-67. DOI: 10.1016/0041-0101(75)90196-8. View

16.

Beress R, Beress L, Wunderer G . Purification and characterisation of four polypeptides with neurotoxic activity from Condylactis aurantiaca. Hoppe Seylers Z Physiol Chem. 1976; 357(3):409-14. DOI: 10.1515/bchm2.1976.357.1.409. View

17.

NORTON T, Shibata S, Kashiwagi M, Bentley J . Isolation and characterization of the cardiotonic polypeptide anthopleurin-A from the sea anemone Anthopleura xanthogrammica. J Pharm Sci. 1976; 65(9):1368-74. DOI: 10.1002/jps.2600650927. View

18.

Shibata S, NORTON T, Izumi T, Matsuo T, Katsuki S . A polypeptide (AP-A) from sea anemone (Anthopleura xanthogrammica) with potent positive inotropic action. J Pharmacol Exp Ther. 1976; 199(2):298-309. View

19.

Bergman C, Dubois J, Rojas E, Rathmayer W . Decreased rate of sodium conductance inactivation in the node of Ranvier induced by a polypeptide toxin from sea anemone. Biochim Biophys Acta. 1976; 455(1):173-84. DOI: 10.1016/0005-2736(76)90162-0. View

20.

Hille B . Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977; 69(4):497-515. PMC: 2215053. DOI: 10.1085/jgp.69.4.497. View