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

Neuron. 2004 Feb 5;41(3):389-404. doi: 10.1016/s0896-6273(03)00844-4.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • 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
  • Membrane Potentials / genetics
  • Mice
  • Mice, Knockout
  • Motor Activity / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurotoxins / pharmacology
  • Nuclear Matrix-Associated Proteins
  • Odorants
  • Olfactory Bulb / cytology*
  • Olfactory Bulb / metabolism
  • Patch-Clamp Techniques / methods
  • Potassium Channels / deficiency
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / biosynthesis
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Scorpion Venoms
  • Sensory Thresholds / physiology
  • Time Factors
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism
  • ras Proteins / genetics
  • ras Proteins / metabolism
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism

Substances

  • 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