Margatoxin is a non-selective inhibitor of human Kv1.3 K+ channels

  • Toxicon. 2014 Sep;87:6-16. doi: 10.1016/j.toxicon.2014.05.002.
Adam Bartok  1 ,  Agnes Toth  2 ,  Sandor Somodi  3 ,  Tibor G Szanto  4 ,  Peter Hajdu  5 ,  Gyorgy Panyi  6 ,  Zoltan Varga  7
Affiliations
  • 1. Department of Biophysics and Cell Biology, University of Debrecen, Faculty of Medicine, 98 Nagyerdei krt., Debrecen 4032, Hungary. Electronic address: [email protected].
  • 2. Department of Biophysics and Cell Biology, University of Debrecen, Faculty of Medicine, 98 Nagyerdei krt., Debrecen 4032, Hungary. Electronic address: [email protected].
  • 3. Division of Metabolic Diseases, Department of Internal Medicine, University of Debrecen, 98 Nagyerdei krt., Debrecen 4032, Hungary. Electronic address: [email protected].
  • 4. Department of Biophysics and Cell Biology, University of Debrecen, Faculty of Medicine, 98 Nagyerdei krt., Debrecen 4032, Hungary. Electronic address: [email protected].
  • 5. Department of Biophysics and Cell Biology, University of Debrecen, Faculty of Dentistry, 98 Nagyerdei krt., Debrecen 4032, Hungary. Electronic address: [email protected].
  • 6. Department of Biophysics and Cell Biology, University of Debrecen, Faculty of Medicine, 98 Nagyerdei krt., Debrecen 4032, Hungary; MTA-DE Cell Biology and Signaling Research Group, 4032 Debrecen, Egyetem tér 1, Hungary. Electronic address: http://biophys.med.unideb.hu/en/node/311.
  • 7. Department of Biophysics and Cell Biology, University of Debrecen, Faculty of Medicine, 98 Nagyerdei krt., Debrecen 4032, Hungary. Electronic address: [email protected].
PMID: 24878374 DOI: 10.1016/j.toxicon.2014.05.002
Abstract

Margatoxin (MgTx), an alpha-KTx scorpion toxin, is considered a selective inhibitor of the Kv1.3K + channel. This peptide is widely used in ion channel research; however, a comprehensive study of its selectivity with electrophysiological methods has not been published yet. The lack of selectivity might lead to undesired side effects upon therapeutic application or may lead to incorrect conclusion regarding the role of a particular ion channel in a physiological or pathophysiological response either in vitro or in vivo. Using the patch-clamp technique we characterized the selectivity profile of MgTx using L929 cells expressing mKv1.1 channels, human peripheral lymphocytes expressing Kv1.3 channels and transiently transfected tsA201 cells expressing hKv1.1, hKv1.2, hKv1.3, hKv1.4-IR, hKv1.5, hKv1.6, hKv1.7, rKv2.1, Shaker-IR, hERG, hKCa1.1, hKCa3.1 and hNav1.5 channels. MgTx is indeed a high affinity inhibitor of Kv1.3 (Kd = 11.7 pM) but is not selective, it inhibits the Kv1.2 channel with similar affinity (Kd = 6.4 pM) and Kv1.1 in the nanomolar range (Kd = 4.2 nM). Based on our comprehensive data MgTX has to be considered a non-selective Kv1.3 inhibitor, and thus, experiments aiming at elucidating the significance of Kv1.3 in in vitro or in vivo physiological responses have to be carefully evaluated.

Keywords
Kv1.2; Kv1.3; Margatoxin; MgTx; Non-selective.
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