A NEW K-SUBUNIT TO SPECIFICALLY ENHANCE KV2.2 (CDRK) EXPRESSION( CHANNEL BETA)

Cloned K+ channel beta subunits are hydrophilic proteins which associa te to pore-forming alpha subunits of the Shaker subfamily. The resulti ng alpha beta heteromultimers K+ channels have inactivation kinetics s ignificantly more rapid than those of the corresponding alpha homomult imers. This paper reports the cloning and the brain localization of mK v beta(4) (m for mouse), a new beta subunit. This new beta subunit is highly expressed in the nervous system but is also present in other ti ssues such as kidney. In contrast with other beta subunits, coexpressi on of the mKv beta(4) subunit with alpha subunits of Shaker-type K+ ch annel does not modify the kinetic properties or voltage-dependence of these channels in Xenopus oocytes. Instead, mKv beta(4) associates to Kv2.2 (CDRK), a Shab K+ channel, to specifically enhance (a factor of up to 6) its expression level without changing its elementary conducta nce or kinetics. It is without effect on another closely related Shab K+ channel Kv2.1 (DRK1). Chimeras between Kv2.1 and Kv2.2 indicate tha t the COOH-terminal end of the Kv2.2 protein is essential for its mKv beta(4) sensitivity. The functional results associated with the observ ation of the co-localization of mKv beta(4) and Kv2.2 transcripts in m ost brain areas strongly suggest that both subunits interact in vivo t o form a slowly-inactivating K+ channel. A chaperone-like effect of mK v beta(4) seems to permit the integration of a larger number of Kv2.2 channels at the plasma membrane.