Participation of Kv1 channels in control of membrane excitability and burst generation in mesencephalic V neurons.
The function and biophysical properties of low threshold Kv1 current in control of membrane resonance, subthreshold oscillations, and bursting in mesencephalic V neurons (Mes V) were examined in rat brain stem slices (P8-P12) using whole cell current and voltage patch-clamp methods. alpha-dendrotoxin application, a toxin with high specificity for Kv1.1, 1.2, and 1.6 channels, showed the presence of a low-threshold K(+) current that activated rapidly around -50 mV and was relatively noninactivating over a 1-s period and had a V(1/2)max of -36.2 mV. Other toxins, specific for individual channels containing either Kv 1.1, 1.2, or 1.3 alpha-subunits, were applied individually, or in combination, and showed that Kv1 channels are heteromeric, composed of combinations of subunits. In current-clamp mode, toxin application transformed the high-frequency resonant properties of the membrane into a low-pass filter and concomitantly reduced the frequency of the subthreshold membrane oscillations. During this period, rhythmical bursting was transformed into low-frequency tonic discharge. Interestingly, in a subset of neurons that did not show bursting, low doses of alpha-dendrotoxin (alpha-DTX) sufficient to block 50% of the low threshold Kv1 channels induced bursting and increased the resonant peak impedance and subthreshold oscillations, which was replicated with computer simulation. This suggests that a critical balance between inward and outward currents is necessary for bursting. This was replicated with computer simulation. Single cell RT-PCR and immunohistochemical methods confirmed the presence of Kv1.1, 1.2, and 1.6 alpha-subunits in Mes V neurons. These data indicate that low threshold Kv1 channels are responsible for membrane resonance, contribute to subthreshold oscillations, and are critical for burst generation.
Hsiao
Chie-Fang
CF
Department of Physiological Science, University of California at Los Angeles, Los Angeles, California, USA.
Kaur
Gurvinder
G
Vong
Angela
A
Bawa
Harpreet
H
Chandler
Scott H
SH
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D055592:Biophysical Phenomena / Q000187:drug effects / Q000502:physiology*; D001703:Biophysics; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000166:cytology*; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology; D051637:Shaker Superfamily of Potassium Channels / Q000235:genetics / Q000378:metabolism*
D004546:Elapid Venoms; D010455:Peptides; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; D051637:Shaker Superfamily of Potassium Channels; C081506:dendrotoxin K; C003609:tityustoxin; C020273:dendrotoxin