Novel Wasp Toxin Discriminates between Neuronal and Cardiac Sodium Channels

  1. Eiji Kinoshita1,
  2. Hiroshi Maejima2,
  3. Kaoru Yamaoka1,
  4. Katsuhiro Konno3,
  5. Nobufumi Kawai4,
  6. Eisuke Shimizu5,
  7. Sawana Yokote5,
  8. Hitoshi Nakayama5 and
  9. Issei Seyama1
  1. 1Department of Physiology (E.K., K.Y., I.S.) and 2Institute of Health Sciences (H.M.), School of Medicine, Hiroshima University, Hiroshima, Japan; 3Institute of Biosciences at Rio Claro, Sao Paulo State University, Sao Paulo, Brazil (K.K.); 4Department of Physiology, Jichi Medical School, Tochigi, Japan (N.K.); and 5Department of Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan (E.S., S.Y., H.N.)

    Abstract

    Pompilidotoxins (PMTXs), derived from the venom of solitary wasp has been known to facilitate synaptic transmission in the lobster neuromuscular junction, and a recent further study from rat trigeminal neurons revealed that the toxin slows Na+ channel inactivation without modifying activation process. Here we report that β-PMTX modifies rat brain type II Na+ channel α-subunit (rBII) expressed in human embryonic kidney cells but fails to act on the rat heart α-subunit (rH1) at similar concentrations. We constructed a series of chimeric mutants of rBII and rH1 Na+ channels and compared modification of the steady-state Na+ currents by β-PMTX. We found that a difference in a single amino acid between Glu-1616 in rBII and Gln-1615 in rH1 at the extracellular loop of D4S3-S4 is crucial for the action of β-PMTX. PMTXs, which are small peptides with 13 amino acids, would be a potential tool for exploring a new functional moiety of Na+channels.

    Footnotes

    • Send reprint requests to: Dr. Issei Seyama, Department of Physiology, School of Medicine, Hiroshima University, Kasumi 1–2-3, Hiroshima 734-8551, Japan. E-mail:issei{at}mcai.med.hiroshima-u.ac.jp

    • This work was supported by Grants from the Ministry of Education and Culture of Japan to K.Y. (11470011) and E.K. (11770023); by the research grant for cardiovascular diseases from the Ministry of Health and Welfare to I.S. (11C-1); by Special Coordination Funds for Promoting Science and Technology of the STA of the Japanese Government to N.K.; by grant-in-aid for Scientific Research (12470483) from the Ministry of Education, Science, Sports and Culture of Japan; and a grant from Core Research for Evolutionary Science and Technology of Japan Science and Technology Corporation to H.N.

    • Abbreviations:
      PMTX
      pompilidotoxin
      rBII
      rat brain type II Na+ channel α-subunit
      rH1
      rat heart Na+channel α-subunit
      D
      domain
      S
      segment
      HEK
      human embryonic kidney
      I-V
      current-voltage
      • Received August 21, 2000.
      • Accepted February 27, 2001.
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    1. Molecular Pharmacology June 1, 2001 vol. 59 no. 6 1457-1463
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