Na v s are responsible for the generation and propagation of electrical signals in excitable cells such as neurons and muscle cells. Na v s comprise four domains, each consisting of six helices, aligned across the cell membrane (Figure ). Helices S1 through S4 of each domain further arrange into the voltage sensing domain (VSD). S4 and its gating charge residues can slide in and out of the membrane upon external stimulation, triggering channel gating. Helices S5 and S6 of each domain make the pore domain (PD), where sodium ions permeate with water. S5 is connected to S6 by two additional loops as well as the selectivity filter. The intracellular gate is responsible for the temporary inactivation of the channel after excitation.