Kv1.3 Channel Gene-Targeted Deletion Produces “Super-Smeller Mice” with Altered Glomeruli, Interacting Scaffolding Proteins, and Biophysics

• Published in: Neuron (Cambridge, Mass.) Mass.), 2004-02, Vol.41 (3), p.389-404
• Main Authors: Fadool, D.A, Tucker, K, Perkins, R, Fasciani, G, Thompson, R.N, Parsons, A.D, Overton, J.M, Koni, P.A, Flavell, R.A, Kaczmarek, L.K
• Format: Article
• Language: English
• Subjects: 14-3-3 Proteins; Adaptor Proteins, Vesicular Transport - genetics; Adaptor Proteins, Vesicular Transport - metabolism; Animals; Behavior, Animal; Blotting, Western; Body Weight - genetics; Brain-Derived Neurotrophic Factor - pharmacology; Calcium Channels - genetics; Calcium Channels - metabolism; Cell culture; Cells, Cultured; Densitometry; Differential Threshold; Discrimination (Psychology); Dose-Response Relationship, Drug; Drinking - genetics; Electric Stimulation; Embryo, Mammalian; Energy Intake - genetics; Excitability; Exploratory Behavior; Gene Deletion; GRB10 Adaptor Protein; Habituation, Psychophysiologic - genetics; Humans; Insulin - pharmacology; Kidney; Kinetics; Kv1.3 Potassium Channel; Kv3.1 gene; Light; Membrane potential; Membrane Potentials - drug effects; Membrane Potentials - genetics; Mice; Mice, Knockout; Mitral cells; Motor Activity - genetics; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural coding; Neurons; Neurons - drug effects; Neurons - physiology; Neurotoxins - pharmacology; Nuclear Matrix-Associated Proteins; Odorants; Olfaction; Olfactory bulb; Olfactory Bulb - cytology; Olfactory Bulb - metabolism; Patch-Clamp Techniques - methods; Phosphorylation; Potassium; Potassium Channels - deficiency; Potassium Channels - genetics; Potassium Channels - metabolism; Potassium Channels, Voltage-Gated; Protein interaction; Proteins; Proteins - genetics; Proteins - metabolism; ras Proteins - genetics; ras Proteins - metabolism; Receptor, trkB - genetics; Receptor, trkB - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; Rodents; Scorpion Venoms; Sensory Thresholds - physiology; Signal transduction; src-Family Kinases - genetics; src-Family Kinases - metabolism; Time Factors; Tyrosine; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(03)00844-4

Mice with gene-targeted deletion of the Kv1.3 channel were generated to study its role in olfactory function. Potassium currents in olfactory bulb mitral cells from Kv1.3 null mice have slow inactivation kinetics, a modified voltage dependence, and a dampened C-type inactivation and fail to be modulated by activators of receptor tyrosine signaling cascades. Kv1.3 deletion increases expression of scaffolding proteins that normally regulate the channel through protein-protein interactions. Kv1.3−/− mice have a 1,000- to 10,000-fold lower threshold for detection of odors and an increased ability to discriminate between odorants. In accordance with this heightened sense of smell, Kv1.3−/− mice have glomeruli or olfactory coding units that are smaller and more numerous than those of wild-type mice. These data suggest that Kv1.3 plays a far more reaching role in signal transduction, development, and olfactory coding than that of the classically defined role of a potassium channel—to shape excitability by influencing membrane potential.