Charybdotoxin and margatoxin acting on the human voltage-gated potassium channel h Kv1.3 and its H399N mutant: An experimental and computational comparison Article

Nikouee, A, Khabiri, M, Grissmer, S et al. (2012). Charybdotoxin and margatoxin acting on the human voltage-gated potassium channel h Kv1.3 and its H399N mutant: An experimental and computational comparison . JOURNAL OF PHYSICAL CHEMISTRY B, 116(17), 5132-5140. 10.1021/jp2102463

cited authors

  • Nikouee, A; Khabiri, M; Grissmer, S; Ettrich, R

authors

abstract

  • The effect of the pore-blocking peptides charybdotoxin and margatoxin, both scorpion toxins, on currents through human voltage-gated hKv1.3 wild-type and hKv1.3-H399N mutant potassium channels was characterized by the whole-cell patch clamp technique. In the mutant channels, both toxins hardly blocked current through the channels, although they did prevent C-type inactivation by slowing down the current decay during depolarization. Molecular dynamics simulations suggested that the fast current decay in the mutant channel was a consequence of amino acid reorientations behind the selectivity filter and indicated that the rigidity-flexibility in that region played a key role in its interactions with scorpion toxins. A channel with a slightly more flexible selectivity filter region exhibits distinct interactions with scorpion toxins. Our studies suggest that the toxin-channel interactions might partially restore rigidity in the selectivity filter and thereby prevent the structural rearrangements associated with C-type inactivation. © 2012 American Chemical Society.

publication date

  • May 3, 2012

published in

Digital Object Identifier (DOI)

start page

  • 5132

end page

  • 5140

volume

  • 116

issue

  • 17