The inactivation behaviour of voltage-gated K-channels may be determined by association of alpha- and beta-subunits.

Voltage-gated K-channels of the Shaker related subfamily have two subunits, membrane integrated alpha- and peripheral beta-subunits. alpha-Subunits may assemble as tetramers and form in in vitro expression systems functional K-channels. beta-Subunits cannot from channels by themselves. Like for alpha-subunits, the rat nervous system apparently expresses a family of beta-subunit proteins. We have demonstrated that one rat K-channel beta-subunit, Kv beta 1, contains an inactivating domain. Upon association of alpha- and Kv beta 1-subunits, delayed-rectifier type K-channels are converted to rapidly inactivating A-type K-channels. The beta-subunit inactivation domain acts via a ball and chain type mechanism previously proposed for N-type inactivation of alpha-subunits. The association of alpha- and beta-subunits endows the nervous system with an unprecedented flexibility and diversity of K-channels which may play an important role in the regulation of nervous excitability.