Subunit gating resulting from individual protonation events in Kir2 channels

Grigory Maksaev, Michael Bründl-Jirout, Anna Stary-Weinzinger, Eva-Maria Zangerl-Plessl (), Sun-Joo Lee and Colin G. Nichols ()
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Grigory Maksaev: Washington University School of Medicine
Michael Bründl-Jirout: University of Vienna
Anna Stary-Weinzinger: University of Vienna
Eva-Maria Zangerl-Plessl: University of Vienna
Sun-Joo Lee: Washington University School of Medicine
Colin G. Nichols: Washington University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Inwardly rectifying potassium (Kir) channels open at the ‘helix bundle crossing’ (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. Decreasing cytoplasmic pH shifts the probability towards lower conductance levels. Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K+ ion occupancy, and K+ conductance. Ion channel gating and conductance are classically understood as separate processes. The present data reveal how individual protonation events change the electrostatic microenvironment of the pore, resulting in step-wise alterations of ion pooling, and hence conductance, that appear as ‘gated’ substates.

Date: 2023
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DOI: 10.1038/s41467-023-40058-7

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