Separable Kv beta subunit domains alter expression and gating of potassium channels

Kv beta subunits have been shown to affect kinetic properties of voltage-gated K+ channel Kv1 alpha subunits and increase the number of cell surface dendrotoxin-binding sites when coexpressed with Kv1.2. Here, we show that Kv beta 1.2 alters both current expression and gating of Kv alpha 1 channels and that each effect is mediated by a distinct Kv beta 1.2 domain. The Kv beta 1.2 N terminus or Kv alpha 1-blocking domain introduced steady state current block, an apparent negative shift in steady state activation, and a slowing of deactivation along with a dramatic reduction in single channel open probability, N-terminal deletions of Kv beta 1.2 no longer altered channel kinetics but promoted dramatic increases in Kv1.2 current. The conserved Kv beta 1 C terminus or Kv alpha 1 expression domain alone was sufficient to increase the number of functional channels. The same effect was observed with the normally noninactivating subunit, Kv beta 2. By contrast, Kv1.5 currents were reduced when coexpressed with either the Kv beta 1 C terminus or Kv beta 2, indicating that the Kv alpha 1 expression domain has Kv alpha 1 isoform-specific effects. Our results demonstrate that Kv beta subunits consist of two domains that are separable on the basis of both primary structure and functional modulation of voltage-gated K+ channels.