Androctonus toxins targeting voltage-gated sodium channels

Abstract

The Androctonus genus constitutes a serious threat to human health in Northern Africa and Southwest Asia because some of the Androctonus subspecies produce the most dangerous venoms for mammals. These venoms have provided several high selective affinity ligands, which specifically interact with sodium, potassium, chloride, and calcium channels. However, the vast majority of lethal toxins, even present in the venom at few percent, is active on voltage-gated sodium (Na v) channels and is responsible of almost the whole venom toxicity in mice by subcutaneous injection. During the last four decades, an increasing amount of data was published on the isolation, chemical, pharmacological, and immunological characterization of several structurally distinct families of these extremely active Androctonus toxins, which induce different biological answers when applied to Na v channels. These toxins have been further extensively used to study the functioning and decipher the topology of Na v channels. This chapter reviews the current knowledge on Androctonus toxins active on Na v channels only, at the structural, biological, and immunological level. The organization of their gene and mRNA precursor will also be approached.