Comparison of binding and block produced by alternatively spliced Kv beta 1 subunits

Voltage-gated K+ (Kv) channels consist of alpha subunits complexed with cytoplasmic Kv beta subunits. Kv beta 1 subunits enhance the inactivation of currents expressed by the Kv1 alpha subunit subfamily. Binding has been demonstrated between the C terminus of Kv beta 1.1 and a conserved segment of the N terminus of Kv1.4, Kv1.5, and Shaher alpha subunits. Here we have examined the interaction and functional properties of two alternatively spliced human Kv beta subunits, 1.2 and 1.3, with Kv alpha subunits 1.1, 1.2, 1.4, and 1.5. In the yeast two hybrid assay, we found that both Kv beta subunits interact specifically through their conserved C-terminal domains with the N termini of each Kv alpha subunit. In functional experiments, we found differences in modulation of Kv1 alpha subunit currents that we attribute to the unique N-terminal domains of the two Kv beta subunits. Both Kv beta subunits act as open channel blockers at physiological membrane potentials, but hKv beta 1.2 is a more potent blocker than hKv beta 1.3 of Kv1.1, Kv1.2, Kv1.4, and Kv1.5. Moreover, hKv beta 1.2 is sensitive to redox conditions, whereas hKv beta 1.3 is not. We suggest that different Kv beta subunits extend the range over which distinct Kv1 alpha subunits are modulated and may provide a variable mechanism for adjusting K+ currents in response to alterations in cellular conditions.