1. Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds.
- Author
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Finol-Urdaneta RK, Belovanovic A, Micic-Vicovac M, Kinsella GK, McArthur JR, and Al-Sabi A
- Subjects
- Animals, Conus Snail chemistry, Cyanobacteria chemistry, Ganglia, Spinal cytology, Ganglia, Spinal drug effects, Humans, Marine Toxins therapeutic use, Neurons drug effects, Neurons metabolism, Potassium Channel Blockers therapeutic use, Sea Anemones chemistry, Shaker Superfamily of Potassium Channels metabolism, Channelopathies drug therapy, Marine Toxins pharmacology, Potassium Channel Blockers pharmacology, Shaker Superfamily of Potassium Channels antagonists & inhibitors
- Abstract
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.
- Published
- 2020
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