Potassium Channels Blockers from the Venom ofAndroctonus mauretanicus mauretanicus

Abstract

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 (SKCa, Kv4.x, and Kv1.x K+ channel families). In this paper, we summarize our work on these toxin/channel interactions.

In vitro studies with renal proximal tubule cells show direct cytotoxicity of Androctonus australis hector scorpion venom triggered by oxidative stress, caspase activation and apoptosis

“…Several types of voltage-gated K + channels are specifically present in renal proximal tubules, including Kv1.10 and KVLQT1 (unlike other nephron segments), and may be blocked (or activated) by components in scorpion venom [29, 30]. Indeed, Kv1.10 is reported blocked by Charybdotoxin (ChTX) from Leiurus quinquestriatus [3].…”

Scorpion toxin peptide action at the ion channel subunit level

“…Kv channels also encompass several subfamilies, such as the Ether-a-go-go-Related Gene (ERG) channels, as part of the ethera-go-go gene (EAG) group (Jimenez-Vargas et al, 2012a). Potassium channels typically have inhibitory effects and act to reduce cellular excitability, such as promoting cell repolarisation after action potential firing (Martin-Eauclaire and Bougis, 2012). K þ channel toxins (KTx), usually short-chain peptides, can broadly influence physiological function, including modulation of neuronal activity, neurotransmitter release and hormonal secretion, lymphocyte activation, muscle contractility, and the cardiac cycle (du Plessis et al, 2008).…”

“…Previous reviews have focused on the structural, computational, and molecular analysis of scorpion venom components and ion channel interactions (Smith et al, 2014;Gurevitz et al, 2014), as well as functional comparison of their actions on ion channels. Although some reviews have outlined a broad overview of SCTX peptide action Quintero-Hernandez et al, 2013;du Plessis et al, 2008), the majority have provided relatively detailed information of SCTX action within particular ion channel subfamilies, such as sodium channels Gordon et al, 2007;Pedraza Escalona and Possani, 2013;Pucca et al, 2015a;Gilchrist and Bosmans, 2012;Gordon and Gurevitz, 2003), potassium channels MartinEauclaire and Bougis, 2012;Jimenez-Vargas et al, 2012a;Bartok et al, 2015;Yu et al, 2016;Bougis and Martin-Eauclaire, 2015;Yang et al, 2015;Wang et al, 2014;Wanke and Restano-Cassulini, 2007), and to a lesser extent, calcium Norton and McDonough, 2008;Ramos-Franco and Fill, 2016), and chloride channels Dardevet et al, 2015). This review establishes a comprehensive comparison of the broad range of functionally-validated SCTX peptide actions across the breadth of ion channel families.…”

“…Stings from the Moroccan black scorpion Androctonus mauretanicus mauretanicus for example, have an 8% mortality rate in children under 10 years old (Martin-Eauclaire and Bougis, 2012). With envenomation, pain and swelling at the site is often followed by paraesthesia and hyperalgesia lasting hours, with possible numbness and tingling lasting days.…”

Neuropathophysiological Effect and Immuno-Inflammatory Response Induced by Kaliotoxin of <b><i>Androctonus</i></b> Scorpion Venom

“…Their purification and chemical, pharmacological, and immunological characterizations have been extensively studied [19]. However, their impact on the induced pathophysiological effect and immuno-inflammatory response has not been deeply studied yet.…”