Animal Toxins Acting on Voltage-Gated Potassium Channels

Abstract

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 Ca(2+). 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 beta-strands, helices, or a mixture of both. The main architectural motifs thereof are referred to as alpha/beta 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.

Estudo clínico-epidemiológico, laboratorial e de vulnerabilidade dos acidentes escorpiônicos atendidos no Hospital Municipal de Santarém - Pará

“…Recently, Guerrero-Vargas et al, 2012, described 12 new sodium channel toxins. This venom has also three already identified toxins that inhibit voltage-gated potassium channels: Tc1, Tc30 and Tc32 (Mouhat et al, 2008;Batista et al, 2002b. It's possible that toxins produced by T. obscurus venom, from the region of Santar em, presented effects in human cerebellum granular cells.…”

“…Esta subfamília tem maior ou menor especificidade e está amplamente distribuída, estando presente em membranas de células do cérebro (Kv1.1.e Kv1.4; Kv1.6 e Kv1.8), do sistema nervoso periférico (Kv1.1 e Kv 1.2), do coração (Kv1.1,Kv1.2; Kv1.4 a Kv 1.8), do músculo liso (kv1.2 e Kv. 1.5), do pâncreas (kv 1.1. a Kv1.3), do pulmão (Kv1.3 a Kv1.7), do rim ( Kv1.5 a 1.8), da retina (Kv 1.1. e Kv 1.2), assim como encontra-se presente em células hematopoiéticas, linfócitos e osteoclastos (Kv1.3) (Mouhat et al,2008). As isoformas Kv1.1 a Kv1.3 são alvo da ação de venenos de escorpiões (Mouhat et al,2008).…”

“…1.5), do pâncreas (kv 1.1. a Kv1.3), do pulmão (Kv1.3 a Kv1.7), do rim ( Kv1.5 a 1.8), da retina (Kv 1.1. e Kv 1.2), assim como encontra-se presente em células hematopoiéticas, linfócitos e osteoclastos (Kv1.3) (Mouhat et al,2008). As isoformas Kv1.1 a Kv1.3 são alvo da ação de venenos de escorpiões (Mouhat et al,2008).…”

“…Toxinas de aranhas e escorpiões foram relatadas como bloqueadores específicos para as 3 isoformas. A família KQT ou kv7, codificada por cinco genes, não tem, até o momento, nenhum ligante natural isolado (Mouhat et al, 2008).…”

“…Até o momento já foram isoladas três toxinas do veneno desta espécie que atuam nos canais do tipo Shaker de potássio: Tc1, TC 30 e Tc 32 (Batista et al, 2002b;Mouhat et al, 2008).…”