Kvβ1 Subunit Binding Specific for Shaker-Related Potassium Channel α Subunits

1989). Kv channels may form ␣ 4 ␤ 4 heteromultimers in vivo (Parcej et al., 1992). Recently, we and others have Zentrum fü r Molekulare Neurobiologie Institut fü r Neurale Signalverarbeitung described the primary sequences of several bovine, rat, and human ␤ subunit cDNAs (Scott et al. Coexpression of some of the cloned Kv␤ Federal Republic of Germany subunits with Kv1␣ subunits conferred rapid A-type in-activation on noninactivating Kv1 channels (delayed rec-Summary tifiers) in expression systems in vitro. Apparently, certain Kv␣ and Kv␤ subunits utilize inac-Voltage-activated potassium (Kv) channels from mam-tivating domains that have similar properties. A-type Kv malian brain are hetero-oligomers containing ␣ and ␤ channel ␣ subunits harbor within their amino-terminal subunits. Coexpression of Kv1␣ and Kv␤1 subunits sequence an inactivating domain that can rapidly block confers rapid A-type inactivation on noninactivating the internal mouth of the channel upon depolarization potassium channels (delayed rectifiers) in expression of the membrane (Hoshi et al., 1990; Ruppersberg et systems in vitro. We have delineated a Kv1.5 amino-al., 1991). A ball-and-chain type mechanism has been terminal region of up to 90 amino acids (residues 112– proposed to explain this amino-terminal (N-type) inacti-201) that is sufficient for interactions of Kv1.5␣ and vation of A-type Kv␣ subunits (Zagotta et al., 1990). Kv␤1 Kv␤1 subunits. Within this region of the Kv1.5 amino subunits also contain an amino-terminal inactivating do-terminus (residues 193–201), a Kv␤1 interaction site main (" ␤-ball ") with structural similarity to the " ␣-ball " necessary for Kv␤1-mediated rapid inactivation of (Heinemann et al., 1994; Rettig et al., 1994). Both ␣ and Kv1.5 currents was detected. This interaction site mo-␤ subunits may provide an inactivating N-type ball do-tif (FYE/QLGE/DEAM/L) is found exclusively in the main for the formation of heteromultimeric A-type Kv Shaker-related subfamily (Kv1). The results show that channels. Therefore, the assembly of different combina-hetero-oligomerization between ␣ and Kv␤1 subunits tions of ␣/␤ Kv channel subunits may considerably in-is restricted to Shaker-related potassium channel ␣ crease the complexity and diversity of A-type Kv subunits. channels. In theory, if any combination between Kv␣ and Kv␤ Introduction subunits were possible, an almost infinite number of structurally and functionally distinct Kv channels could Voltage-activated potassium (Kv) channels are impor-be created. Thus, it is important to understand the mo-tant determinants of membrane excitability that are in-lecular rules that determine their assembly into hetero-volved in the regulation of wave forms and frequencies multimeric Kv channels. It has …