Topology and subunit arrangements in different voltage-gated ion channels. (A) Topology (top) and arrangement of the four subunits (bottom) of Kv channels with a central, common pore (made up of the four S5-S6 pore domains, one from each subunit) and four separate voltage-sensing domains (made up of S1-S4 in each subunit; Long et al., 2005). K⁺ flows through the common central pore. A similar topology and arrangement are for NaV and CaV, but the four subunits are covalently linked into one long polypeptide with four six-TM domains. (B) Topology (top) and arrangement of the two subunits (bottom) of Hv1 channels (Ramsey et al., 2006; Sasaki et al., 2006). The two Hv1 subunits are held together by the coiled-coil formed by the two C termini (Li et al., 2010). Each subunit has its own H⁺ conduction pathway (Koch et al., 2008; Tombola et al., 2008). His140 and His193 that coordinate Zn²⁺ in WT Hv1 channels are labeled. (C) Deletion of the C termini (Hv1-ΔC) separates the subunits into fully functional, monomeric Hv1 channels (Koch et al., 2008; Tombola et al., 2008).