μ-Conotoxins Modulating Sodium Currents in Pain

The Conus genus includes around 500 species of marine mollusks with a peculiar 9 production of venomous peptides known as conotoxins (CTX). Each species is able to produce up 10 to 200 different biological active peptides. Common structure of CTX is the low number of 11 aminoacids stabilized by disulfide bridges and post-translational modifications that give rise to 12 different isoforms. μ and μO-CTX are two isoforms that specifically target voltage-gated sodium 13 channels. These, by inducing the entrance of sodium ions in the cell, modulate the neuronal 14 excitability by depolarizing plasma membrane and propagating the action potential. 15 Hyperxcitability and mutations of sodium channels are responsible for perception and transmission 16 of inflammatory and neuropathic pain states. In this review, we describe the current knowledge of 17 μ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their 18 potential therapeutic use as analgesic compounds in the clinical management of pain conditions. 19