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The Journal of Neuroscience, September 1, 2001, 21(17):6553-6560

Modulation of Excitability by alpha -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 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 ~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.

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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