Kv1.3 channel gene-targeted deletion produces "Super-Smeller Mice" with altered glomeruli, interacting scaffolding proteins, and biophysics.
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.
Fadool
D A
DA
Department of Biological Science, Programs in Neuroscience and Molecular Biophysics, The Florida State University, Tallahassee, FL 32306, USA. dfadool@bio.fsu.edu
Tucker
K
K
Perkins
R
R
Fasciani
G
G
Thompson
R N
RN
Parsons
A D
AD
Overton
J M
JM
Koni
P A
PA
Flavell
R A
RA
Kaczmarek
L K
LK
D048948:14-3-3 Proteins; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003720:Densitometry; D004056:Differential Threshold; D004192:Discrimination, Psychological; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000235:genetics; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D002149:Energy Intake / Q000235:genetics; D005106:Exploratory Behavior; D051383:GRB10 Adaptor Protein; D017353:Gene Deletion; D006185:Habituation, Psychophysiologic / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D051664:Kv1.3 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D034521:Nuclear Matrix-Associated Proteins; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology* / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012604:Scorpion Venoms; D012684:Sensory Thresholds / Q000502:physiology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
D048948:14-3-3 Proteins; D033942:Adaptor Proteins, Vesicular Transport; D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; C495959:Grb10 protein, mouse; D007328:Insulin; C496973:KCNA3 protein, human; C496974:Kcna3 protein, mouse; D051664:Kv1.3 Potassium Channel; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D034521:Nuclear Matrix-Associated Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D012333:RNA, Messenger; D012604:Scorpion Venoms; C033652:postsynaptic density proteins; D051383:GRB10 Adaptor Protein; C077910:margatoxin; D014446:Tyrosine 3-Monooxygenase; D020813:Receptor, trkB; D019061:src-Family Kinases; D018631:ras Proteins