Tamapin, a Venom Peptide from the Indian Red Scorpion (Mesobuthus tamulus) That Targets Small Conductance Ca2+-activated K+ Channels and Afterhyperpolarization Currents in Central Neurons*

  1. Peter N. StrongtOe,tOlm
  1. From the tOaDepartment of Physiology and the tOdWellcome Laboratory for Molecular Pharmacology, University College London, London WC1E 6BT, United Kingdom, the tObMax Planck Institute for Experimental Medicine, 37075 Göttingen, Germany, the tOeDepartment of Pediatrics and Neonatal Medicine, Imperial College School of Medicine, London W12 0NN, United Kingdom, the tOhNational University of Singapore, Singapore 119260, the tOjHaffkine Institute, Mumbai 400012, India, and the tOlDivision of Biomedical Sciences, Sheffield Hallam University, Sheffield S1 1WB, United Kingdom

Abstract

The biophysical properties of small conductance Ca2+-activated K+ (SK) channels are well suited to underlie afterhyperpolarizations (AHPs) shaping the firing patterns of a conspicuous number of central and peripheral neurons. We have identified a new scorpion toxin (tamapin) that binds to SK channels with high affinity and inhibits SK channel-mediated currents in pyramidal neurons of the hippocampus as well as in cell lines expressing distinct SK channel subunits. This toxin distinguished between the SK channels underlying the apamin-sensitiveI AHP and the Ca2+-activated K+ channels mediating the slowI AHP (sIAHP) in hippocampal neurons. Compared with related scorpion toxins, tamapin displayed a unique, remarkable selectivity for SK2 versus SK1 (∼1750-fold) and SK3 (∼70-fold) channels and is the most potent SK2 channel blocker characterized so far (IC50 for SK2 channels = 24 pm). Tamapin will facilitate the characterization of the subunit composition of native SK channels and help determine their involvement in electrical and biochemical signaling.

  • Abbreviations:
    SK
    small conductance Ca2+-activated K+
    AHP
    afterhyperpolarization
    HPLC
    high performance liquid chromatography
    IK
    intermediate conductance Ca2+-activated K+
    • Received June 28, 2002.
    • Revision received September 10, 2002.
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    1. First Published on September 17, 2002 doi: 10.1074/jbc.M206465200 The Journal of Biological Chemistry 277, 46101-46109.
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