Hydrophobic residues in S6 segments of nav contribute to the fast inactivation gate

Abstract

Fast inactivation is essential for physiological function. The sodium current inactivation has been proposed to be a closure of the conduction pathway by the IFM motif between the DIII-DIV linker. However, recent structural data show that the IFM motif is far away from the pore and not likely to block the conduction pathway directly. Searching for a potential inactivation gate, we performed comparative sequence/structure analysis of Navs. We identified two hydrophobic amino acids from each S6 helices that can potentially serve as the gate.