Separable Kvβ subunit domains alter expression and gating of potassium channels

Abstract

Kvβ subunits have been shown to affect kinetic properties of voltage- gated K+ channel Kv1α subunits and increase the number of cell surface dendrotoxin-binding sites when coexpressed with Kv1.2. Here, we show that Kvβ1.2 alters both current expression and gating of Kvα1 channels and that each effect is mediated by a distinct Kvβ1.2 domain. The Kvβ1.2 N terminus or Kvα1-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 Kvβ1.2 no longer altered channel kinetics but promoted dramatic increases in Kv1.2 current. The conserved Kvβ1 C terminus or Kvα1 expression domain alone was sufficient to increase the number of functional channels. The same effect was observed with the normally noninactivating subunit, Kvβ2. By contrast, Kv1.5 currents were reduced when coexpressed with either the Kvβ1 C terminus or Kvβ2, indicating that the Kvα1 expression domain has Kvα1 isoform-specific effects. Our results demonstrate that Kvβ subunits consist of two domains that are separable on the basis of both primary structure and functional modulation of voltage-gated K+ channels.