Modulation of excitability by alpha-dendrotoxin-sensitive potassium channels in neocortical pyramidal neurons

J Neurosci. 2001 Sep 1;21(17):6553-60. doi: 10.1523/JNEUROSCI.21-17-06553.2001.


Many neurons transduce synaptic inputs into action potentials (APs) according to rules that reflect their intrinsic membrane properties. Voltage-gated potassium channels, being numerous and diverse constituents of neuronal membrane, are important participants in neuronal excitability and thus in synaptic integration. Here we address the role of dendrotoxin-sensitive "D-type" potassium channels in the excitability of large pyramidal neurons in layer 5 of the rat neocortex. Low concentrations of 4-aminopyridine or alpha-dendrotoxin (alpha-DTX) dramatically increased excitability: the firing threshold for action potentials was hyperpolarized by 4-8 mV, and the firing frequency during a 1-sec-long 500 pA somatic current step was doubled. In nucleated outside-out patches pulled from the soma, alpha-DTX reversibly blocked a slowly inactivating potassium current that comprised approximately 6% of the total. This current first turned on at voltages just hyperpolarized to the threshold for spiking and activated steeply with depolarization. By assaying alpha-DTX-sensitive current in outside-out patches pulled from the axon and primary apical dendrite, it was found that this current was concentrated near the soma. We conclude that alpha-DTX-sensitive channels are present on large layer 5 pyramidal neurons at relatively low density, but their strategic location close to the site of action potential initiation in the axon may ensure that they have a disproportionate effect on neuronal excitability. Modulation of this class of channel would generate a powerful upregulation or downregulation of neuronal output after the integration of synaptic inputs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials / drug effects
  • Animals
  • Axons / metabolism
  • Dendrites / metabolism
  • Dose-Response Relationship, Drug
  • Elapid Venoms / pharmacology*
  • In Vitro Techniques
  • Neocortex / cytology
  • Neocortex / drug effects
  • Neocortex / metabolism*
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Potassium Channel Blockers
  • Potassium Channels / classification
  • Potassium Channels / metabolism*
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / metabolism*
  • Rats
  • Rats, Wistar
  • Sensory Thresholds / drug effects
  • Sensory Thresholds / physiology
  • Tetraethylammonium / pharmacology


  • Elapid Venoms
  • Potassium Channel Blockers
  • Potassium Channels
  • Tetraethylammonium
  • dendrotoxin
  • 4-Aminopyridine
  • Potassium