Recombinant Kv1.3 potassium channels stabilize tonic firing of cultured rat hippocampal neurons.
We transfected cultured hippocampal neurons with the cDNA of the voltage-gated K+ channel Kv1.3 to investigate the mechanisms by which a specific ion channel influences excitability. In transfected neurons under voltage clamp we observed an additional outward current that was blocked selectively by margatoxin. Under current-clamp conditions, Kv1.3-expressing neurons fired tonically over a wide range of stimulation intensity. In non-transfected neurons, or in Kv1.3-expressing cells blocked with margatoxin, only a few action potentials were elicited before a stationary depolarized state was reached. We attribute the specific effect of Kv1.3 to its particularly slow deactivation near the resting potential. A computational model showed that a continuous outwards current arises in Kv1.3-expressing neurons during the interspike intervals. It expands the dynamic range so that these neurons still fire tonically at stimulus current intensities at which non-transfected cells have already been driven into a stationary depolarized state.
Kupper
Jürgen
J
Department of Membrane and Neurophysics, Max Planck Institute of Biochemistry, Martinsried, Germany.
Prinz
Astrid A
AA
Fromherz
Peter
P
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression / Q000502:physiology; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology*; D007202:Indicators and Reagents / Q000378:metabolism; D051664:Kv1.3 Potassium Channel; D008164:Luminescent Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012604:Scorpion Venoms
D007202:Indicators and Reagents; C496975:Kcna3 protein, rat; D051664:Kv1.3 Potassium Channel; D008164:Luminescent Proteins; D009498:Neurotoxins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D012604:Scorpion Venoms; D049452:Green Fluorescent Proteins; C077910:margatoxin