A constricted opening in Kir channels does not impede potassium conduction

• Published in: Nature communications Vol. 11; no. 1; pp. 3024 - 13
• Main Authors: Black, Katrina A., He, Sitong, Jin, Ruitao, Miller, David M., Bolla, Jani R., Clarke, Oliver B., Johnson, Paul, Windley, Monique, Burns, Christopher J., Hill, Adam P., Laver, Derek, Robinson, Carol V., Smith, Brian J., Gulbis, Jacqueline M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.06.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/45/535; 631/57; 82/58; Channel gating; Channels; Computer simulation; Conduction; Conformation; Cytosol; Cytosol - chemistry; Cytosol - metabolism; Dehydration; Electric Conductivity; Electric Impedance; Free energy; G Protein-Coupled Inwardly-Rectifying Potassium Channels - chemistry; G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics; G Protein-Coupled Inwardly-Rectifying Potassium Channels - metabolism; Humanities and Social Sciences; Humans; Intracellular; Ion Transport; Ions; Ions - chemistry; Ions - metabolism; Model testing; Molecular dynamics; Molecular Dynamics Simulation; multidisciplinary; Potassium; Potassium - chemistry; Potassium - metabolism; Potassium channels; Potassium channels (inwardly-rectifying); Potassium currents; Protein Conformation; Science; Science (multidisciplinary); Water - metabolism; Water chemistry
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16842-0

The canonical mechanistic model explaining potassium channel gating is of a conformational change that alternately dilates and constricts a collar-like intracellular entrance to the pore. It is based on the premise that K + ions maintain a complete hydration shell while passing between the transmembrane cavity and cytosol, which must be accommodated. To put the canonical model to the test, we locked the conformation of a Kir K + channel to prevent widening of the narrow collar. Unexpectedly, conduction was unimpaired in the locked channels. In parallel, we employed all-atom molecular dynamics to simulate K + ions moving along the conduction pathway between the lower cavity and cytosol. During simulations, the constriction did not significantly widen. Instead, transient loss of some water molecules facilitated K + permeation through the collar. The low free energy barrier to partial dehydration in the absence of conformational change indicates Kir channels are not gated by the canonical mechanism. The transition between conducting and non-conducting states of K + channels has been explained by conformational changes at the intracellular entrance to the conduction pathway. Here authors demonstrate that control over K + currents in Kir channels is not explained by the canonical pore-gating model, as conduction is not impaired by a constricted inner helix bundle.