title: Regulation of Shaker K+ channel inactivation gating by the cAMP-dependent protein kinase.
abstract: In response to depolarization of the membrane potential, Shaker K+ channels undergo a series of voltage-dependent conformational changes, from resting to open conformations followed by a rapid transition into a long-lived closed conformation, the N-type inactivated state. Application of phosphatases to the cytoplasmic side of Shaker channels in excised inside-out patches slows N-type inactivation gating. Subsequent application of the purified catalytic subunit of the cAMP-dependent protein kinase (PKA) and ATP reverses the effect, accelerating N-type inactivation back to its initial rapid rate. Macroscopic and single-channel experiments indicate that N-type inactivation is selectively modulated. There was little or no effect on the voltage dependence and kinetics of activation. Comparison of site-directed mutant channels shows that a C-terminal consensus site for PKA phosphorylation is responsible for the modulation. Since a cell's integrative characteristics can be determined by the rate of inactivation of its voltage-dependent channels, modulation of these rates by phosphorylation is likely to have functional consequences.
authors.affiliation: Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305.
authors.forename: P
authors.initials: P
authors.lastname: Drain
authors.forename: A E
authors.initials: AE
authors.lastname: Dubin
authors.forename: R W
authors.initials: RW
authors.lastname: Aldrich
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000409:Alanine; D000469:Alkaline Phosphatase / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D017931:DNA Primers; D004330:Drosophila; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D014644:Genetic Variation; D015640:Ion Channel Gating / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D017433:Protein Structure, Secondary; D012694:Serine; D013997:Time Factors; D014158:Transcription, Genetic; D014981:Xenopus
chemical_list: D017931:DNA Primers; D015221:Potassium Channels; D012694:Serine; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D000469:Alkaline Phosphatase; D000409:Alanine