Kv beta 2 inhibits the Kv beta 1-mediated inactivation of K+ channels in transfected mammalian cells

Cloned auxiliary beta-subunits (e.g. Kv beta 1) modulate the kinetic properties of the pore-forming cu subunits of a subset of Shaker-like potassium channels. Coexpression of the alpha-subunit and Kv beta 2, however, induces little change in channel properties. Since more than one beta-subunit has been found in individual K+ channel complexes and expression patterns of different beta-subunits overlap in vivo, it is important to test the possible physical and/or functional interaction(s) between different beta-subunits. In this report, we show that both Kv beta 2 and Kv beta 1 recognize the same region on the pore-forming alpha-subunits of the Kv1 Shaker-like potassium channels. In the absence of alpha-subunits the Kv beta 2 polypeptide interacts with additional beta-subunit(s) to form either a homomultimer with Kv beta 2 or a heteromultimer with Kv beta 1, When coexpressing alpha-subunits and Kv beta 1 in the presence of Kv beta 2, we find that Kv beta 2 is capable of inhibiting the Kv beta 1-mediated inactivation, Using deletion analysis, we have localized the minimal interaction region that is sufficient for Kv beta 2 to associate with both alpha-subunits and Kv beta 1. This mapped minimal interaction region is necessary and sufficient for inhibiting the Kv beta 1-mediated inactivation, consistent with the notion that the inhibitory activity of Kv beta 2 results from the coassembly of Kv beta 2 with compatible alpha-subunits and possibly with Kv beta 1. Together, these results provide biochemical evidence that Kv beta 2 may profoundly alter the inactivation activity of another beta-subunit by either differential subunit assembly or by competing for binding sites on alpha-subunits, which indicates that Kv beta 2 is capable of serving as an important determinant in regulating the kinetic properties of K+ currents.