Interactions among inactivating and noninactivating Kv beta subunits, and Kv alpha 1.2, produce potassium currents with intermediate inactivation

Experiments were carried out to determine whether coinjection of Kv alpha 1.2 with inactivating and noninactivating Kv beta subunits would produce currents with intermediate kinetics and channel complexes containing a mixture of these subunits. Upon coexpression with a saturating amount of Kv beta 1.2 and increasing levels of a noninactivating deletion mutant of Kv beta 1.2, we show that macroscopic Kv alpha 1.2 currents have levels of fractional inactivation and inactivation time constants that are intermediate between those obtained with either the inactivating Kv beta 1.2 or the noninactivating Kv beta 1.2 mutant. We also find that coexpression of Kv alpha 1.2 with saturating amounts of Kv beta 1.2 and the deletion mutant produces a population of single channels with properties intermediate to either the inactivating or noninactivating parental phenotype. Our data can best be explained by the presence of an intermediate population of heterooligomeric channels consisting of Kv alpha 1.2 with different combinations of both types of subunits. Since Kv alpha 1.2 subunits coexist in cells with inactivating and noninactivating Kv beta subunits, our findings suggest that heterooligomeric assembly of these subunits occurs to increase the range of K+ current kinetics and expression levels.