MOLECULAR-PROPERTIES OF VOLTAGE-GATED K+ CHANNELS

Subfamilies of voltage-activated K+ channels (Kv1-4) contribute to con trolling neuron excitability and the underlying functional parameters. Genes encoding the multiple a subunits from each of these protein gro ups have been cloned, expressed and the resultant distinct K+ currents characterized. The predicted amino acid sequences showed that each a subunit contains six putative membrane-spanning alpha-helical segments (S1-6), with one (S4) being deemed responsible for the channels' volt age sensing. Additionally, there is an H5 region, of incompletely defi ned structure, that traverses the membrane and forms the ion pore; res idues therein responsible for K+ selectivity have been identified. Sus ceptibility of certain K+ currents produced by the Shaker-related subf amily (Kv1) to inhibition by alpha-dendrotoxin has allowed purificatio n of authentic K+ channels from mammalian brain. These are large (M(r) similar to 400 kD), octomeric sialoglycoproteins composed of alpha an d beta subunits in a stoichiometry of (alpha)(4) beta)(4), with subtyp es being created by combinations of subunit isoforms. Subsequent cloni ng of the genes for beta(1), beta(2) and beta(3) subunits revealed nov el sequences for these hydrophilic proteins that are postulated to be associated with the alpha subunits on the inner side of the membrane. Coexpression of beta(1) and Kv1.4 subunits demonstrated that this auxi liary beta protein accelerates the inactivation of the K+ current, a s triking effect mediated by an N-terminal moiety. Models are presented that indicate the functional domains pinpointed in the channel protein s.