Distinct functional stoichiometry of potassium channel β subunits

Shaker-type potassium channels play important roles in determining the electrical excitability of cells. The native channel complex is thought to be formed by four pore-forming α subunits that provide four interaction sites for auxiliary modulatory Kvβ subunits. Because Kvβ subunits possess diverse modulatory activities including either up-regulation or down-regulation of potassium currents, differential assembly of the α–β complex could give rise to diverse current properties. However, the detailed physical and functional stoichiometry of the α–β complex remains unknown. Kvβ1 subunits reduce potassium currents through inactivation, whereas Kvβ2 subunits enhance potassium currents by inhibiting the Kvβ1-mediated inactivation and at the same time by promoting the surface expression of certain potassium channels. In this report we show that Kvβ1 and Kvβ2 of the Shaker-type potassium channels display distinct functional stoichiometry to interact with the Kv1 α subunits, a subfamily of Shaker-type potassium channels. The interaction of Kvβ1 subunits with α subunits is consistent with the α₄β_n model, where n equals 0, 1, 2, 3, or 4, depending upon the relative concentration of α and β subunits. The α₄β_n stoichiometry allows for gradual changes of the Kvβ1-mediated inactivation. In contrast, Kvβ2 subunits self-associate to form oligomers and interact with the α subunits via α₄β₄ stoichiometry, which permits effective multivalent associations with α subunits. Such distinct functional stoichiometry of Kvβ1 and Kvβ2 provides a molecular mechanism that is well suited to their contrasting activities of up-regulation or down-regulation of potassium currents.