Progress in understanding slow inactivation speeds up

Abstract

A new study reveals that conformational flexibility in the pore of a voltage-gated sodium channel may underlie slow inactivation.

Figure 1.

Proposed structural features of conductive and inactivated bacterial Nav channel states. (A) Schematic view of an eNav channel pore-forming α-subunit; β-subunits are not depicted for clarity. (B) Schematic view of a BacNav channel subunit. (C) Extracellular views of available BacNav channel crystal structures proposed to have selectivity filters captured in a conductive (green) or inactivated (red) state. Conductive selectivity filter structures are represented by NavAb_I217C (PDB accession no. 3RVY, shown in green) or NavMs (PDB accession no. 5HVD); inactivated selectivity filter structures are represented by NavAb_WT (PDB accession no. 4EKW, shown in red) or NavRh (PDB accession no. 4DXW). (D) Schematic summary of the results reported by Chatterjee et al. (2018) obtained from EPR and DEER studies on a panel of NavSp1 channel spin-labeled mutants. VSDs are not depicted for clarity as mutations studied in NavSp1 targeted the turret loop, P1 helix, and P2 helix. The authors proposed that a dynamic, asymmetric pore module represents the inactivated state (depicted in red), whereas a much less dynamic, more symmetric pore module represents the conductive state (depicted in green).