A versatile functional interaction between electrically silent K subunits and K7 potassium channels.

Voltage-gated K (K) 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 channels (KS), however, are unable to conduct currents on their own. It has been assumed that these KS must obligatorily assemble with subunits from the K2 family into heterotetrameric channels, thereby giving rise to currents distinct from those of homomeric K2 channels. Herein, we show that KS subunits indeed also modulate the activity, biophysical properties and surface expression of recombinant K7 isoforms in a subunit-specific manner. Employing co-immunoprecipitation, and proximity labelling, we unveil the spatial coexistence of KS and K7 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 KS and K7 interaction may occur. Our findings demonstrate that K cross-family interaction is much more versatile than previously thought-possibly serving nature to shape potassium conductance to the needs of individual cell types.