The Apamin-Sensitive Ca2+-Dependent K+ Channel: Molecular Properties, Differentiation, Involvement in Muscle Disease, and Endogeneous Ligands in Mammalian Brain

  • M. Lazdunski
  • G. Romey
  • H. Schmid-Antomarchi
  • J. F. Renaud
  • C. Mourre
  • M. Hugues
  • M. Fosset
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 83)


Apamin is a neurotoxin extracted from bee venom (Habermann 1972). It is a polypeptide of 18 amino acids with two disulfide bridges (Fig. 1). It is the only polypeptide neurotoxin, as far as we know, that crosses the blood-brain barrier. Analysis of the structure-function relationships of this toxin has shown that two of the 18 amino acids in the sequence have particular importance for the action of the toxin; they are Arg-13 and Arg-14 (Vincent et al. 1975). These two residues seem to be essential elements of the active site of the toxin. Chemical modifications elsewhere in the sequence may decrease the toxicity of the polypeptide, but do not suppress its biologic activity. Cumulative chemical modifications — of the amino group and of the imidazole of His-18 for example — may, however, abolish the activity of the toxin (Vincent et al. 1975). Solid phase synthesis of apamin and analogs has been carried out (Cosand and Merrifield 1977; Granier et al. 1978). This approach has confirmed that the active site of apamin comprises the two residues Arg-13 and Arg-14. The exact three-dimensional structure of the toxin remains unknown. However, recent solution analysis of apamin by NMR techniques has suggested that the toxin is highly ordered with an α-helical core and regions of β-type turns (Bystrov et al. 1980; Wemmer and Kallenbach 1983).


Myotonic Muscular Dystrophy Undifferentiated PC12 Cell Myotonic Muscular Dystrophy Patient Disuccinimidyl Suberate Repetitive Action Potential 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • M. Lazdunski
  • G. Romey
  • H. Schmid-Antomarchi
  • J. F. Renaud
  • C. Mourre
  • M. Hugues
  • M. Fosset

There are no affiliations available

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