ABSTRACT
Venoms allow snakes to capture prey as well as defend against predators and other threats. Being crucial for snake survival, venoms have been fine-tuned by evolutionary pressures to disrupt essential physiological systems in bitten victims. Thus, different snake venoms may evoke neurotoxic, myotoxic, hemotoxic or cardiotoxic effects that are mediated by specialized toxins. Snake neurotoxins modulate the activity of ion channels and other proteins in peripheral nerves and skeletal muscles to produce weakness, suffocation, paralysis, fasciculations and pain. These neurotoxins are primarily peptides and proteins commonly found in venoms from elapid and colubrid snakes and only rarely in venoms of pitvipers. Many of these toxins share common scaffolds due to conserved disulfide bridges, which underlie their stability both in the venom gland and in envenomed tissues. In addition, to produce a robust effect, functional domains in these folds vary, endowing the different toxins with high potency and selectivity towards diverse targets. These pharmacological properties make snake neurotoxins invaluable molecular probes for studying ion channels. Indeed, these toxins, including α-bungarotoxin and α-dendrotoxin, were fundamental in understanding the structure, function and physiological roles of nicotinic acetylcholine receptors (nACHR) and Kv1 channels, respectively. While the nACHRs and voltage-gated potassium channels, as well as the neuromuscular junction in general, serve as canonical sites of activity, other ion channels and synapses have recently emerged as targets for snake neurotoxins; toxins that affect acid-sensing ion channels (ASICs), P2Xs, GABAA, and voltage-gated sodium channels will be reviewed here. These toxins, mainly described in the past few years, evoke diverse nociceptive, inflammatory and neuromuscular effects. Thus, these unique snake venom toxins can provide insights into the molecular basis for hallmark responses to snake envenomations as well as the activation mechanism of targeted ion channels.
