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Animal Toxins Acting on Voltage-Gated Potassium Channels

[ Vol. 14 , Issue. 24 ]


Stephanie Mouhat, Nicolas Andreotti, Besma Jouirou and Jean-Marc Sabatier   Pages 2503 - 2518 ( 16 )


Animal venoms are rich natural sources of bioactive compounds, including peptide toxins acting on the various types of ion channels, i.e. K+, Na+, Cl- and Ca2+. Among K+ channel-acting toxins, those selective for voltage-gated K+ (Kv) channels are widely represented and have been isolated from the venoms of numerous animal species, such as scorpions, sea anemones, snakes, marine cone snails and spiders. The toxins characterized hitherto contain between 22 and 60 amino acid residues, and are cross-linked by two to four disulfide bridges. Depending on their types of fold, toxins can be classified in eight structural categories, which showed a combination of β-strands, helices, or a mixture of both. The main architectural motifs thereof are referred to as α/β scaffold and inhibitor cystine knot (ICK). A detailed analysis of toxin structures and pharmacological selectivities indicates that toxins exhibiting a similar type of fold can exert their action on several subtypes of Kv channels, whereas a particular Kv channel can be targeted by toxins that possess unrelated folds. Therefore, it appears that the ability of structurally divergent toxins to interact with a particular Kv channel relies onto a similar spatial distribution of amino acid residues that are key to the toxin-channel interaction (rather than the type of toxin fold). The diversity of Kv channel blockers and their therapeutic value in the potential treatment of a number of specific human diseases, especially autoimmune disorders, inflammatory neuropathies and cancer, are reviewed.


Animal toxins,voltage-gated K+ channels,K+ channel blockers,anti-tumor agents,immunomodulation,autoimmune diseases,neuropathies


, , , Ingenierie des peptides a visee therapeutique, ERT 62, Universite de la Mediterranee - Ambrilia Biopharma Inc., Faculte de Medecine Nord, Bvd P. Dramard, 13916–Marseille Cedex 20, France.

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