title: Phosphorylation of K+ channels at single residues regulates memory formation.
abstract: Phosphorylation is a ubiquitous post-translational modification of proteins, and a known physiological regulator of K+ channel function. Phosphorylation of K()channels by kinases has long been presumed to regulate neuronal processing and behavior. Although circumstantial evidence has accumulated from behavioral studies of vertebrates and invertebrates, the contribution to memory of single phosphorylation sites on K+ channels has never been reported. We have used gene targeting in mice to inactivate protein kinase A substrate residues in the fast-inactivating subunit Kv4.2 (T38A mutants), and in the small-conductance Ca2+ -activated subunit SK1 (S105A mutants). Both manipulations perturbed a specific form of memory, leaving others intact. T38A mutants had enhanced spatial memory for at least 4 wk after training, whereas performance in three tests of fear memory was unaffected. S105A mutants were impaired in passive avoidance memory, sparing fear, and spatial memory. Together with recent findings that excitability governs the participation of neurons in a memory circuit, this result suggests that the memory type supported by neurons may depend critically on the phosphorylation of specific K+ channels at single residues.
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Vernon
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London W12 ONN, United Kingdom.
authors.forename: Elaine E
authors.initials: EE
authors.lastname: Irvine
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom Dart Neuroscience, 12278 Scripps Summit Drive, San Diego, California 92131, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Peters
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Jeshmi
authors.initials: J
authors.lastname: Jeyabalan
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom Centre for the Cellular Basis of Behaviour, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 9NU, United Kingdom karl.giese@kcl.ac.uk.
authors.forename: K Peter
authors.initials: KP
authors.lastname: Giese
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004597:Electroshock; D005239:Fear / Q000502:physiology*; D005260:Female; D018390:Gene Targeting; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D065852:Spatial Memory / Q000502:physiology*
chemical_list: C496895:Kcnn1 protein, mouse; D051672:Shal Potassium Channels; D051640:Small-Conductance Calcium-Activated Potassium Channels; D017868:Cyclic AMP-Dependent Protein Kinases