Voltage-gated ion channels are ubiquitous to excitable cells, i.e., are found in the heart, in the nervous system and in many other organs. They fulfill a wide variety of biological functions and are therefore sensitive to a large number of modulating factors, e.g., action of drugs or anesthetics, alteration of the membrane lipids embedding them, etc. Similarly, mutations of these channels can give rise to familial genetic diseases, called channelopathies.
We characterize the effect of specific basic residues mutations located in the sensing domain. Mutations perturb the VSD structure and trigger the appearance of state-dependent leak currents. The simulations unveil the key elementary molecular processes involved in these so-called “omega” currents.