Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy.
Department of Sciences, University of Basilicata, 75100 Potenza, Italy.
Mar Drugs. 2017 Sep 22;15(10):295. doi: 10.3390/md15100295.
The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX). Each species is able to produce up to 200 different biological active peptides. Common structure of CTX is the low number of amino acids stabilized by disulfide bridges and post-translational modifications that give rise to different isoforms. µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain conditions.
圆锥螺属包括约 500 种海洋软体动物，它们能够产生具有生物活性的毒液肽，称为 Conotoxin（CTX）。每种物种都能产生多达 200 种不同的生物活性肽。CTX 的常见结构是由二硫键稳定的少量氨基酸和翻译后修饰，从而产生不同的同工型。µ 和 µO-CTX 是两种同工型，它们专门针对电压门控钠离子通道。这些通道通过诱导钠离子进入细胞，通过去极化质膜和传播动作电位来调节神经元兴奋性。钠离子通道的过度兴奋和突变负责炎症和神经性疼痛状态的感知和传递。在这篇综述中，我们描述了 µ-CTX 与不同的钠离子通道亚型相互作用的最新知识，包括其作用机制及其作为镇痛化合物在疼痛疾病的临床管理中的潜在治疗用途。
