Title: Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB.

Authors: W N Zagotta, T Hoshi, R W Aldrich

Journal, date & volume: Science, 1990 Oct 26 , 250, 568-71

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/2122520

Abstract
Site-directed mutagenesis experiments have suggested a model for the inactivation mechanism of Shaker potassium channels from Drosophila melanogaster. In this model, the first 20 amino acids form a cytoplasmic domain that interacts with the open channel to cause inactivation. The model was tested by the internal application of a synthetic peptide, with the sequence of the first 20 residues of the ShB alternatively spliced variant, to noninactivating mutant channels expressed in Xenopus oocytes. The peptide restored inactivation in a concentration-dependent manner. Like normal inactivation, peptide-induced inactivation was not noticeably voltage-dependent. Trypsin-treated peptide and peptides with sequences derived from the first 20 residues of noninactivating mutants did not restore inactivation. These results support the proposal that inactivation occurs by a cytoplasmic domain that occludes the ion-conducting pore of the channel.