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Molecular Pharmacology

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Research ArticleArticle

Heteropodatoxins: Peptides Isolated from Spider Venom that Block Kv4.2 Potassium Channels

Michael C. Sanguinetti, Janice H. Johnson, Lance G. Hammerland, Paul R. Kelbaugh, Robert A. Volkmann, Nicholas A. Saccomano and Alan L. Mueller
Molecular Pharmacology March 1997, 51 (3) 491-498;
Michael C. Sanguinetti
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Janice H. Johnson
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Lance G. Hammerland
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Paul R. Kelbaugh
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Robert A. Volkmann
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Nicholas A. Saccomano
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Alan L. Mueller
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Abstract

Toxins isolated from scorpion, snake, and spider venoms are valuable tools to probe the physiologic function and structure of ion channels. In this study, we have isolated three new toxins (heteropodatoxins) from the venom of a spider, Heteropoda venatoria. These toxins are structurally similar peptides of 29 to 32 amino acids and share sequence homology with hanatoxins isolated from the venom of a Chilean tarantula. The heteropodatoxins prolonged the action-potential duration of isolated rat ventricular myocytes, suggesting that the peptides block K+ currents. The effect of toxins on cardiac K+ currents were studied using voltage clamp techniques. The toxins blocked the transient outward K+ current but not other K+ currents in isolated rat cardiac myocytes. The mechanism of block was studied further using Kv4.2, a cloned channel believed to underlie transient outward K+ current in rat myocytes. The toxins blocked Kv4.2 current expressed in Xenopus laevis oocytes in a voltage-dependent manner, with less block at more positive potentials. In addition, the toxins slowed the time course of current activation and inactivation and shifted the voltage dependence of current inactivation to more positive potentials. The heteropodatoxins represent new pharmacologic probes to study the role of Kv4.2 channels in cardiac and neural tissue.

Footnotes

  • Send reprint requests to: Michael Sanguinetti, Ph.D., Division of Cardiology, University of Utah, Bldg. 533, Room 4220, Salt Lake City, UT 84112.

  • ↵1 Current affiliation: Division of Cardiology, Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112.

  • Abbreviations:
    HpTx
    heteropodatoxin
    Ito1
    voltage-dependent transient outward potassium current
    TFA
    trifluoroacetic acid
    HPLC
    high performance liquid chromatography
    PTC
    phenylthiocarbamyl
    • Received September 26, 1996.
    • Accepted November 14, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology
Vol. 51, Issue 3
1 Mar 1997
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Research ArticleArticle

Heteropodatoxins: Peptides Isolated from Spider Venom that Block Kv4.2 Potassium Channels

Michael C. Sanguinetti, Janice H. Johnson, Lance G. Hammerland, Paul R. Kelbaugh, Robert A. Volkmann, Nicholas A. Saccomano and Alan L. Mueller
Molecular Pharmacology March 1, 1997, 51 (3) 491-498;

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Research ArticleArticle

Heteropodatoxins: Peptides Isolated from Spider Venom that Block Kv4.2 Potassium Channels

Michael C. Sanguinetti, Janice H. Johnson, Lance G. Hammerland, Paul R. Kelbaugh, Robert A. Volkmann, Nicholas A. Saccomano and Alan L. Mueller
Molecular Pharmacology March 1, 1997, 51 (3) 491-498;
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