conotoxins targeting neuronal voltage-gated sodium channel subtypes potential analgesics个目标神经元电压门控钠通道亚型潜在的止痛剂.pdfVIP

Toxins 2012, 4, 1236-1260; doi:10.3390/toxins4111236 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Conotoxins Targeting Neuronal Voltage-Gated Sodium Channel Subtypes: Potential Analgesics? Oliver Knapp †, Jeffrey R. McArthur † and David J. Adams * Health Innovations Research Institute, RMIT University, Melbourne, Victoria 3083, Australia; E-Mails: oliver.knapp@.au (O.K.); jeffrey.mcarthur@.au (J.R.M.) † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: david.adams@.au; Tel.: +61-3-9925-6606. Received: 10 October 2012; in revised form: 5 November 2012 / Accepted: 5 November 2012 / Published: 8 November 2012 Abstract: Voltage-gated sodium channels (VGSC) are the primary mediators of electrical signal amplification and propagation in excitable cells. VGSC subtypes are diverse, with different biophysical and pharmacological properties, and varied tissue distribution. Altered VGSC expression and/or increased VGSC activity in sensory neurons is characteristic of inflammatory and neuropathic pain states. Therefore, VGSC modulators could be used in prospective analgesic compounds. VGSCs have specific binding sites for four conotoxin families: μ-, μO-, δ- and ί-conotoxins. Various studies have identified that the binding site of these peptide toxins is restricted to well-defined areas or domains. To date, only the μ- and μO-family exhibit analgesic properties in animal pain models. This review will focus on conotoxins fr