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The Journal of Neuroscience, September 1, 2001, 21(17):6553-6560
Modulation of Excitability by -Dendrotoxin-Sensitive Potassium
Channels in Neocortical Pyramidal Neurons
John M.
Bekkers and
Andrew J.
Delaney
Division of Neuroscience, John Curtin School of Medical Research,
Australian National University, Canberra, ACT 0200, Australia
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 -dendrotoxin
( -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, -DTX
reversibly blocked a slowly inactivating potassium current that
comprised ~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 -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 -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.
Key words:
action potential; D-current; dendrite; dendrotoxin; neocortex; potassium channel; pyramidal neuron
Copyright © 2001 Society for Neuroscience 0270-6474/01/21176553-08$05.00/0
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