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Two novel sodium channel inhibitors from Heriaeus melloteei spider venom differentially interacting with mammalian

Bert Billen1, Alexander Vassilevski, Anton Nikolsky

  • 1Laboratory of Toxicology, University of Leuven, Campus Gasthuisberg, O&N 2, P.O. Box 922, Herestraat 49, 3000 Leuven, Belgium.

Toxicon : Official Journal of the International Society on Toxinology
|July 9, 2008
PubMed

Insights

Two novel spider toxins, Hm-1 and Hm-2, from Heriaeus melloteei venom inhibit mammalian voltage-gated sodium channels (Na(+) channels). They decrease Na(+) current amplitude and alter inactivation, offering insights into toxin-channel interactions.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Neuroscience

Background:

  • Spider venom contains diverse bioactive peptides.
  • Voltage-gated sodium channels (Na(+) channels) are crucial for nerve and muscle function.
  • Understanding toxin interactions with Na(+) channels is vital for drug discovery and neuroscience.

Purpose of the Study:

  • To isolate and characterize novel polypeptide toxins from Heriaeus melloteei crab spider venom.
  • To investigate the effects of these toxins on mammalian voltage-gated Na(+) channels.

Main Methods:

  • Isolation and purification of toxins Hm-1 and Hm-2 from spider venom.
  • Amino acid sequencing and structural analysis (disulfide bonds, potential knot motif).
  • Electrophysiological recordings (two-electrode voltage clamp) to assess effects on Na(+) currents in cells expressing Na(V)1.4 channels.

Main Results:

  • Two new toxins, Hm-1 (37 amino acids) and Hm-2 (40 amino acids), were identified.
  • Both toxins significantly inhibited Na(+) current peak amplitude (IC(50) values: Hm-1 = 336.4 nM, Hm-2 = 154.8 nM).
  • Hm-1 and Hm-2 negatively shifted the steady-state inactivation of Na(+) channels without affecting activation or fast inactivation kinetics.

Conclusions:

  • Hm-1 and Hm-2 are potent inhibitors of mammalian voltage-gated Na(+) channels.
  • Their distinct effects on inactivation suggest novel mechanisms of action.
  • These toxins provide valuable structural insights into polypeptide inhibitor interactions with Na(+) channels.

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