Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Numerous point mutations in sodium channel genes have been identified in pyrethroid-resistant insect species, and many have been confirmed to reduce or abolish sensitivity of channels expressed in Xenopus oocytes to pyrethroids. Recently, several novel mutations were reported in sodium channel genes of pyrethroid-r...

The persistent tetrodotoxin (TTX)-sensitive sodium current, detected in neurons of many regions of mammalian brains, is associated with many essential neuronal activities, including boosting of excitatory synaptic inputs, acceleration of firing rates, and promotion of oscillatory neuronal activities. However, the origin and molecular basis of the persistent current have remained controversial f...

A series of imidazol-1-ylethylindazole sodium channel ligands were developed and optimized for sodium channel inhibition and in vitro neuroprotective activity. The molecules exhibited displacement of a radiolabeled sodium channel ligand and selectivity for blockade of the inactivated state of cloned neuronal Nav channels. Metabolically stable analogue 6 was able to protect retinal ganglion cell...

The crystal structure of the open conformation of a bacterial voltage-gated sodium channel pore from Magnetococcus sp. (NaVMs) has provided the basis for a molecular dynamics study defining the channel's full ion translocation pathway and conductance process, selectivity, electrophysiological characteristics, and ion-binding sites. Microsecond molecular dynamics simulations permitted a complete...