%0 Journal Article
%T Potassium Channels Blockers from the Venom of Androctonus mauretanicus mauretanicus
%A Marie-France Martin-Eauclaire
%A Pierre E. Bougis
%J Journal of Toxicology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/103608
%X K+ channels selectively transport K+ ions across cell membranes and play a key role in regulating the physiology of excitable and nonexcitable cells. Their activation allows the cell to repolarize after action potential firing and reduces excitability, whereas channel inhibition increases excitability. In eukaryotes, the pharmacology and pore topology of several structural classes of K+ channels have been well characterized in the past two decades. This information has come about through the extensive use of scorpion toxins. We have participated in the isolation and in the characterization of several structurally distinct families of scorpion toxin peptides exhibiting different K+ channel blocking functions. In particular, the venom from the Moroccan scorpion Androctonus mauretanicus mauretanicus provided several high-affinity blockers selective for diverse K+ channels ( S K C a , K v 4.x, and K v 1.x K+ channel families). In this paper, we summarize our work on these toxin/channel interactions. 1. The Scorpion Venom Content Scorpion venoms are very complex mixtures of molecules, constituting a diverse, naturally occurring peptide library, with most peptides displaying different kinds of biological activity [1, 2]. These peptides can specifically bind to a variety of pharmacological targets, in particular ion channels, resulting in neurotoxic effects. Toxins modulating Na+, K+, Ca++, and Cl£¿ currents have been described in scorpion venoms [2]. Toxins that are highly lethal for mammals modify voltage-gated Na+ (Nav) currents in excitable cells and are referred to as ¡°Nav channel long-chain toxin.¡± These toxins are single-chain, small, basic peptides (60- to 75-amino-acid residue chain generally folded by four disulfide bridges). They have been described as ¦Á- or ¦Â-toxins due to their binding site on Nav channels as well as to their pharmacological effects [1, 3]. ¦Á-Toxins bind in a voltage-dependent manner on the voltage sensor of the Nav channel domain IV and inhibit the inactivation phase of the action potential. ¦Â-Toxins act on the channel activation phase by binding to extracellular loops located preferentially on the voltage sensor of the Nav channel domain II (but also occasionally of domain III) [1, 3¨C6]. Another class of scorpion toxins has also been widely studied, even if these toxins are devoid of serious lethal effect. They block different K+ channel subtypes (some of them in the picomolar range) and are so-called ¡°K+ channel toxins¡± [1, 2, 7]. They are usually shorter than Nav channel toxins but are structurally closely related to them.
%U http://www.hindawi.com/journals/jt/2012/103608/