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Kv2.1 Potassium Channels Regulate Repetitive Burst Firing in Extratelencephalic Neocortical Pyramidal Neurons.

Greg S Newkirk1, Dongxu Guan2, Nikolai Dembrow1,3

  • 1Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.

Cerebral Cortex (New York, N.Y. : 1991)
|August 26, 2021
PubMed
Summary

Potassium Kv2 channels regulate neuronal bursting in the motor cortex. Blocking these channels promotes repetitive firing and abnormal brain rhythms, suggesting a key role in preventing epilepsy.

Keywords:
Thy1-h neuronafterdepolarizationcortical rhythmepilepsyguangxitoxin

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Area of Science:

  • Neuroscience
  • Cellular Electrophysiology
  • Computational Neuroscience

Background:

  • Neuronal burst firing influences coincidence detection and cortical rhythmicity.
  • Repetitive burst firing in the neocortex can lead to abnormal rhythms, including epilepsy.
  • Outward currents regulating bursting, particularly the fast afterdepolarization (fADP), are not well understood.

Purpose of the Study:

  • To investigate the role of Kv2 channels in regulating fADP and burst firing in layer 5 pyramidal neurons (PNs) from the Thy1-h mouse motor cortex.
  • To determine the expression pattern of Kv2 channel subtypes in these neurons.

Main Methods:

  • Pharmacological block of Kv2 channels using guangxitoxin-1E (GTx).
  • Electrophysiological recordings from Thy1-h mouse motor cortex layer 5 PNs.
  • Immunohistochemistry to identify Kv2.1 and Kv2.2 channel expression.
  • Somatic macropatch recordings to characterize GTx-sensitive currents.
  • Network modeling to simulate the effects of Kv2 channel reduction on circuit activity.

Main Results:

  • Kv2 channel block converted single spike responses to multispike bursts with an enhanced fADP.
  • Thy1-h PNs express Kv2.1 channels, primarily in the perisomatic region.
  • GTx-sensitive current constituted the largest outward current component in somatic macropatches.
  • Kv2 channel block induced repetitive burst firing in ~40% of stimulated PNs and altered frequency-dependent gain.
  • Network models demonstrated that reduced Kv2 conductance in a subset of neurons induced repetitive bursting and seizure-like network activity.

Conclusions:

  • Kv2 channels play a critical role in regulating the onset of bursts and preventing repetitive burst firing in Thy1-h motor cortex PNs.
  • Kv2 channels are crucial for maintaining normal cortical rhythmicity and may represent a therapeutic target for conditions like epilepsy.