Interaction of the Transmembrane Navab Channel with Cholesterol and Lipids in the Membrane

Increased cholesterol levels are associated with multiple pathological conditions. In this work, molecular dynamics simulations were applied to observe the influence of membrane cholesterol levels on a voltage-gated sodium channel. Different lipid compositions to obtain information about the possible effects by which cholesterol influences NavAb channels were studied. Cholesterol was normally not directly interacting with either the closed or inactivated conformation. Cholesterol increased lipid packing implying that it plays a crucial role in restricting lipid movement in the region around 1 nm of the channel in a 1-palmitoyl-2-oeleoyl phosphatidylcholine (POPC) matrix. Our results provide the first computational indication of an indirect modulation of NavAb channels by membrane cholesterol.