Participation of Kv1 Channels in Control of Membrane Excitability and Burst Generation in Mesencephalic V Neurons

J Neurophysiol. 2009 Mar;101(3):1407-18. doi: 10.1152/jn.91053.2008. Epub 2009 Jan 14.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Animals, Newborn
  • Biophysical Phenomena / drug effects
  • Biophysical Phenomena / physiology*
  • Biophysics
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Elapid Venoms / pharmacology
  • Electric Stimulation / methods
  • In Vitro Techniques
  • Mesencephalon / cytology*
  • Models, Neurological
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Scorpion Venoms / pharmacology
  • Shaker Superfamily of Potassium Channels / genetics
  • Shaker Superfamily of Potassium Channels / metabolism*

Substances

  • Elapid Venoms
  • Peptides
  • Potassium Channel Blockers
  • Scorpion Venoms
  • Shaker Superfamily of Potassium Channels
  • dendrotoxin K
  • tityustoxin
  • dendrotoxin