Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds

• Published in: Marine drugs 2020-03, Vol.18 (3), p.173
• Main Authors: Finol-Urdaneta, Rocio K, Belovanovic, Aleksandra, Micic-Vicovac, Milica, Kinsella, Gemma K, McArthur, Jeffrey R, Al-Sabi, Ahmed
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; bioactives; Biological activity; Channelopathies - drug therapy; Channels; conotoxins 2; Conus Snail - chemistry; Cyanobacteria; Cyanobacteria - chemistry; Dorsal root ganglia; Electric fields; Ganglia; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Humans; Ion channels; Ions; kv1; Marine animals; Marine invertebrates; Marine molluscs; Marine organisms; marine toxins; Marine Toxins - pharmacology; Marine Toxins - therapeutic use; Medical treatment; modulators; Neurons - drug effects; Neurons - metabolism; Peptides; Potassium; Potassium Channel Blockers - pharmacology; Potassium Channel Blockers - therapeutic use; potassium channels; Potassium channels (voltage-gated); Profiling; Review; sea anemone toxins; Sea Anemones - chemistry; Selectivity; Shaker Superfamily of Potassium Channels - antagonists & inhibitors; Shaker Superfamily of Potassium Channels - metabolism; Snails; Toxins; Venom
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md18030173

Toxins from marine animals provide molecular tools for the study of many ion channels, including mammalian voltage-gated potassium channels of the Kv1 family. Selectivity profiling and molecular investigation of these toxins have contributed to the development of novel drug leads with therapeutic potential for the treatment of ion channel-related diseases or channelopathies. Here, we review specific peptide and small-molecule marine toxins modulating Kv1 channels and thus cover recent findings of bioactives found in the venoms of marine Gastropod (cone snails), Cnidarian (sea anemones), and small compounds from cyanobacteria. Furthermore, we discuss pivotal advancements at exploiting the interaction of κM-conotoxin RIIIJ and heteromeric Kv1.1/1.2 channels as prevalent neuronal Kv complex. RIIIJ's exquisite Kv1 subtype selectivity underpins a novel and facile functional classification of large-diameter dorsal root ganglion neurons. The vast potential of marine toxins warrants further collaborative efforts and high-throughput approaches aimed at the discovery and profiling of Kv1-targeted bioactives, which will greatly accelerate the development of a thorough molecular toolbox and much-needed therapeutics.