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Ca2+-activated K+ channels of human and rabbit erythrocytes display distinctive patterns of inhibition by venom peptide toxins

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Abstract

Despite recent progress in the molecular characterization of high-conductance Ca2+-activated K+ (maxi-K) channels, the molecular identities of intermediate conductance Ca2+-activated K+ channels, including that of mature erythrocytes, remains unknown. We have used various peptide toxins to characterize the intermediate conductance Ca2+-activated K+ channels (Gardos pathway) of human and rabbit red cells. With studies on K+ transport and on binding of 125I-charybdotoxin (ChTX) and 125I-kaliotoxin (KTX) binding in red cells, we provide evidence for the distinct nature of the red cell Gardos channel among described Ca2+-activated K+ channels based on (i) the characteristic inhibition and binding patterns produced by ChTX analogues, iberiotoxin (IbTX) and IbTX-like ChTX mutants, and KTX (1–37 and 1–38 variants); (ii) the presence of some properties heretofore attributed only to voltage-gated channels, including inhibition of K transport by margatoxin (MgTX) and by stichodactyla toxin (StK); (iii) and the ability of scyllatoxin (ScyTX) and apamin to displace bound 125I-charybdotoxin, a novel property for K+ channels. These unusual pharmacological characteristics suggest a unique structure for the red cell Gardos channel.

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Authors and Affiliations

  1. Departments of Pathology and Laboratory Medicine, The Children's Hospital, 300 Longwood Avenue, 02115, Boston, MA

    C. Brugnara & C. C. Armsby

  2. Department of Internal Medicine, University of Verona, Verona, Italy

    L. De Franceschi

  3. Laboratoires de Neurobiologie and d'Ingenierie des Proteines, Centre National de la Recherche Scientifique, Marseille, France

    M. Crest & M.-F. Martin Euclaire

  4. Molecular Medicine and Renal Units, Beth Israel Hospital and Department of Cell Biology and Medicine, Harvard Medical School, 330 Brookline Avenue, 02215, Boston, MA

    S. L. Alper

Authors
  1. C. Brugnara
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  2. C. C. Armsby
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  3. L. De Franceschi
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  4. M. Crest
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  5. M.-F. Martin Euclaire
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  6. S. L. Alper
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Additional information

We thank Dr. Chris Miller of Brandeis University for generously providing recombinant ChTX mutants, Dr. Maria Garcia of Merck Research Laboratories for MgTX and Dr. Regine Romi of Laboratoire d'Ingenierie des Proteines (Marseille, France) for synthetic KTX,1–37 and KTX,1–38. This research was supported by grant HL-15157 from the National Institutes of Health.

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Brugnara, C., Armsby, C.C., De Franceschi, L. et al. Ca2+-activated K+ channels of human and rabbit erythrocytes display distinctive patterns of inhibition by venom peptide toxins. J. Membarin Biol. 147, 71–82 (1995). https://doi.org/10.1007/BF00235398

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  • DOI: https://doi.org/10.1007/BF00235398

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