Diversification of Potassium Currents in Excitable Cells via Kvβ Proteins

Figures

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  Figure 1. Kv1α4β4 complex structure. (A) Sideview of the Kv1 holochannel structure showing interaction between the pore-forming α tetramer (green) and the intracellular Kvβ tetramer (blue). The intracellular T1 domain of the α subunits serves as a docking platform for the Kvβ subunits. (B,C) Top-down (B) and bottom-up (C) views of the structure shown in (A). Distinct peptides are shown with differential shading. Adapted with the Pymol software using protein database ID 7EJ1.

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  Figure 2. Molecular diversity of Kv1 complexes. Potential interacting subunits are show for Kv1α (top) and Kvβ (bottom) tetrameric structures. Gene names and corresponding proteins are listed. Known splice variants for Kvβ proteins are listed for each Kvβ in parentheses.

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  Figure 3. Proposed influence of the Kvβ1:Kvβ2 functional expression on IKv inactivation and repolarization. Schematic illustration depicting Kv α4β4 channel assembly (left) with possible combinations of Kvβ proteins present in native heteromultimeric structures. (Center) Expected impact of Kvβ stoichiometry on current inactivation rates is exemplified with theoretical trace recordings of depolarization (+++) -evoked whole-cell IKv for cells expressing homogenous channel populations with the Kvβ ratios as indicated. Differential effects of the bound cofactor for β1(4) and β2(4) configurations are shown in dashed blue traces. (Right) Predicted influence of differential Kvβ stochiometries on action potential duration in the presence of low and high cytosolic NAD(P)H:NADP+ ratios.

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  Figure 4. Summary of the Kvβ functional roles. General regulatory features or Kvβ (A) as discussed in Section 2 and Section 3 and the key physiological roles for Kvβ proteins in the central nervous system (CNS), heart, and vasculature (B) as discussed in Section 4, Section 5 and Section 6. Created with BioRender.com (accessed on 2 July 2022).