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PMID: 14766178 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Kv1.3 channel gene-targeted deletion produces "Super-Smeller Mice" with altered glomeruli, interacting scaffolding proteins, and biophysics.

Neuron ·Vol. 41 ·No. 3 ·2004-02-05 ·Pages 389-404

Fadool DA, Tucker K, Perkins R, Fasciani G, Thompson RN, Parsons AD, Overton JM, Koni PA, Flavell RA, Kaczmarek LK

Abstract

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.

MeSH Terms
14-3-3 Proteins Adaptor Proteins, Vesicular Transport/genetics,metabolism Animals Behavior, Animal Blotting, Western Body Weight/genetics Brain-Derived Neurotrophic Factor/pharmacology Calcium Channels/genetics,metabolism Cells, Cultured Densitometry Differential Threshold Discrimination, Psychological Dose-Response Relationship, Drug Drinking/genetics Electric Stimulation Embryo, Mammalian Energy Intake/genetics Exploratory Behavior GRB10 Adaptor Protein Gene Deletion Habituation, Psychophysiologic/genetics Humans Insulin/pharmacology Kidney Kinetics Kv1.3 Potassium Channel Membrane Potentials/drug effects,genetics Mice Mice, Knockout Motor Activity/genetics Nerve Tissue Proteins/genetics,metabolism Neurons/drug effects,physiology Neurotoxins/pharmacology Nuclear Matrix-Associated Proteins Odorants Olfactory Bulb/cytology,metabolism Patch-Clamp Techniques/methods Potassium Channels/deficiency,genetics,metabolism Potassium Channels, Voltage-Gated Proteins/genetics,metabolism RNA, Messenger/biosynthesis Receptor, trkB/genetics,metabolism Reverse Transcriptase Polymerase Chain Reaction/methods Scorpion Venoms Sensory Thresholds/physiology Time Factors Tyrosine 3-Monooxygenase/genetics,metabolism ras Proteins/genetics,metabolism src-Family Kinases/genetics,metabolism
Chemicals
14-3-3 Proteins Adaptor Proteins, Vesicular Transport Brain-Derived Neurotrophic Factor Calcium Channels Grb10 protein, mouse Insulin KCNA3 protein, human Kcna3 protein, mouse Kv1.3 Potassium Channel Nerve Tissue Proteins Neurotoxins Nuclear Matrix-Associated Proteins Potassium Channels Potassium Channels, Voltage-Gated Proteins RNA, Messenger Scorpion Venoms postsynaptic density proteins GRB10 Adaptor Protein margatoxin Tyrosine 3-Monooxygenase Receptor, trkB src-Family Kinases ras Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Fadool D A
Department of Biological Science, Programs in Neuroscience and Molecular Biophysics, The Florida State University, Tallahassee, FL 32306, USA. [email protected]
Tucker K
Perkins R
Fasciani G
Thompson R N
Parsons A D
Overton J M
Koni P A
Flavell R A
Kaczmarek L K
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
0896-6273
DOI
10.1016/s0896-6273(03)00844-4
Email
[email protected]
Published
2004-02-05
Pages
389-404
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2737549
Subset
IM
Grants
NIDCD NIH HHS · DC01919 · United States
NIDCD NIH HHS · R01 DC003387 · United States
NIDCD NIH HHS · R01 DC003387-07A1 · United States
NIDCD NIH HHS · R29 DC003387 · United States
NIDCD NIH HHS · DC03387 · United States
NIDCD NIH HHS · R01 DC001919 · United States
External Links
PubMed source DOI: 10.1016/s0896-6273(03)00844-4 PMC Full Text View journal details
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