Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms

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Acid-sensing ion channels (ASICs) are proton-activated cation channels that are expressed in a variety of neuronal and non-neuronal tissues. As proton-gated channels, they have been implicated in many pathophysiological conditions where pH is perturbed. Venom derived compounds represent the most potent and selective modulators of ASICs described to date, and thus have been invaluable as pharmacological tools to study ASIC structure, function, and biological roles. There are now ten ASIC modulators described from animal venoms, with those from snakes and spiders favouring ASIC1, while the sea anemones preferentially target ASIC3. Some modulators, such as the prototypical ASIC1 modulator PcTx1 have been studied in great detail, while some of the newer members of the club remain largely unstudied. Here we review the current state of knowledge on venom derived ASIC modulators, with a particular focus on their molecular interaction with ASICs, what they have taught us about channel structure, and what they might still reveal about ASIC function and pathophysiological roles.This article is part of the Special Issue entitled ‘Venom-derived Peptides as Pharmacological Tools.’HIGHLIGHTSThe most potent and selective modulators of ASICs have come from animal venoms.ASIC modulators have been isolated from spiders, sea anemones, and snakes.Venom peptides have advanced our understanding of ASIC gating and structure.Venom peptides have helped elucidate the in vitro and in vivo roles of ASICs.Venom-derived modulators of ASICs are likely to play a big role in the future.

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