Voltage-Gated Sodium Channel Inhibition by μ-Conotoxins

mu-Conotoxins are small, potent pore-blocker inhibitors of voltage-gated sodium (Na-V) channels, which have been identified as pharmacological probes and putative leads for analgesic development. A limiting factor in their therapeutic development has been their promiscuity for different Na-V channel subtypes, which can lead to undesirable side-effects. This review will focus on four areas of mu-conotoxin research: (1) mapping the interactions of mu-conotoxins with different Na-V channel subtypes, (2) mu-conotoxin structure-activity relationship studies, (3) observed species selectivity of mu-conotoxins and (4) the effects of mu-conotoxin disulfide connectivity on activity. Our aim is to provide a clear overview of the current status of mu-conotoxin research.