Molecular properties of voltage-gated K+ channels.
Subfamilies of voltage-activated K+ channels (Kv1-4) contribute to controlling neuron excitability and the underlying functional parameters. Genes encoding the multiple alpha subunits from each of these protein groups have been cloned, expressed and the resultant distinct K+ currents characterized. The predicted amino acid sequences showed that each alpha subunit contains six putative membrane-spanning alpha-helical segments (S1-6), with one (S4) being deemed responsible for the channels' voltage sensing. Additionally, there is an H5 region, of incompletely defined structure, that traverses the membrane and forms the ion pore; residues therein responsible for K+ selectively have been identified. Susceptibility of certain K+ currents produced by the Shaker-related subfamily (Kv1) to inhibition by alpha-dendrotoxin has allowed purification of authentic K+ channels from mammalian brain. These are large (M(r) approximately 400 kD), octomeric sialoglycoproteins composed of alpha and beta subunits in a stoichiometry of (alpha)4(beta)4, with subtypes being created by combinations of subunit isoforms. Subsequent cloning of the genes for beta 1, beta 2 and beta 3 subunits revealed novel 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 auxiliary beta protein accelerates the inactivation of the K+ current, a striking effect mediate by an N-terminal moiety. Models are presented that indicate the functional domains pinpointed in the channel proteins.
Dolly
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Department of Biochemistry, Imperial College, London, United Kingdom.
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D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009498:Neurotoxins / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry / Q000502:physiology*; D011487:Protein Conformation; D012910:Snake Venoms; D013329:Structure-Activity Relationship
D009498:Neurotoxins; D010455:Peptides; D015221:Potassium Channels; D012910:Snake Venoms; C081705:dendrotoxin A