THE INACTIVATION BEHAVIOR OF VOLTAGE-GATED K-CHANNELS MAY BE DETERMINED BY ASSOCIATION OF ALPHA-SUBUNIT AND BETA-SUBUNIT

Voltage-gated K-channels of the Shaker related subfamily have two subu nits, membrane integrated alpha- and peripheral beta-subunits. alpha-S ubunits may assemble as tetramers and form in in vitro expression syst ems functional K-channels. beta-Subunits cannot form channels by thems elves. Like for alpha-subunits, the rat nervous system apparently expr esses a family of beta-subunit proteins. We have demonstrated that one rat K-channel beta-subunit, K-v beta 1, contains an inactivating doma in. Upon association of alpha- and K-v beta 1-subunits, delayed-rectif ier type K-channels are converted to rapidly inactivating A-type K-cha nnels. The beta-subunit inactivation domain acts via a ball and chain type mechanism previously proposed for N-type inactivation of alpha-su bunits. 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 excitabi lity.