A Versatile Functional Interaction between Electrically Silent K _V Subunits and K _V 7 Potassium Channels

Voltage-gated K ⁺ (K _V ) channels govern K+-ion flux across cell membranes in response to changes in membrane potential. They are formed by the assembly of four subunits, typically from the same family. Electrically silent K _V channels (K _V S), however, are unable to conduct currents on their own. It has been assumed that these K _V S must obligatorily assemble with subunits from the K _V 2 family into heterotetrameric channels, thereby giving raise to currents distinct from those of homomeric K _V 2 channels.

Herein, we show that K _V S subunits indeed also modulate the activity, biophysical properties and surface expression of recombinant K _V 7 isoforms in a subunit-specific manner. Employing co-immunoprecipitation, and proximity labelling, we unveil the spatial coexistence of K _V S and K _V 7 within a single protein complex. Electrophysiological experiments further indicate functional interaction and probably heterotetramer formation. Finally, single-cell transcriptomic analyses identify native cell types in which this K _V S and K _V 7 interaction may occur. Our finding demonstrate that K _V cross-family interaction is much more versatile than previously thought – possibly serving nature to shape potassium conductance to the needs of individual cell types.