An acid-sensing ion channel is the target for small peptides from the venom of a cone snail

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Catharina Reimers , Cheng-Han Lee , Hubert Kalbacher , Yuemin Tian , Chih-Hsien Hung , Axel Schmidt , Lea Prokop , Silke Kauferstein , Dietrich Mebs , Chih-Cheng Chen , Stefan Gründer

Original publication

Cone snails are amongst the venomous animals with the highest diversity of toxins. Many of these toxins, the conotoxins, are well described and bind with high specificity and high affinity to membrane proteins, in particular ion channels. They are therefore well suited to elucidate the function of these channels and are now important tools of basic science. In addition, they also have therapeutic potential, because they can inspire the design of small molecule drugs. Sometimes, the toxin itself can be used clinically, for example to treat some forms of severe pain.

In a study, which was published in PNAS, researchers from the group of Stefan Gründer at the Institute of Physiology at RWTH Aachen University could show in collaboration with other groups, for example from Aacademia Sinica in Taiwan, that the cone snail Conus textile contains a small peptide in its venom that has a different chemical structure than conotoxins and that is classified as a cono-RFamide. This cono-RFamide binds to acid-sensing ion channel ASIC3, which detects painful acidosis. The cono-RFamide potentiates the response of ASIC3 to acid and acid-induced muscle pain. The study reveals that the venom of cone snails contains other components than conotoxins with specific target molecules and underlines the importance of ASIC3 for the development of some forms of muscle pain.