Abstract
Voltage gated sodium channels are fundamental players in animals physiology. By triggering the depolarization of the lipid membrane they enable generation and propagation of the action potential. The involvement of these channels in numerous pathological conditions makes them relevant target for pharmaceutical intervention. Therefore, modulation of sodium conductance via small molecule binding constitutes a promising strategy to treat a large variety of diseases. However, this approach entails significant challenges: voltage gated sodium channels are complex nanomachines and the details of their workings have only recently started to become clear. Here we review - with emphasis on the computational studies - some of the major milestones in the long-standing search of a quantitative microscopic description of the molecular mechanism and modulation of voltage-gated sodium channels.