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

John M. Bekkers, Andrew J. Delaney

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

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 α-dendrotoxin (α-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, α-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 α-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 α-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.

Original languageEnglish
Pages (from-to)6553-6560
Number of pages8
JournalJournal of Neuroscience
Volume21
Issue number17
Publication statusPublished - 01 Sep 2001

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Pyramidal Cells
Potassium Channels
Action Potentials
Carisoprodol
Axons
Voltage-Gated Potassium Channels
4-Aminopyridine
Membranes
Neocortex
Dendrites
Potassium
Up-Regulation
Down-Regulation
Neurons
dendrotoxin

Cite this

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abstract = "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 α-dendrotoxin (α-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, α-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 α-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 α-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.",
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Modulation of excitability by α-dendrotoxin-sensitive potassium channels in neocortical pyramidal neurons. / Bekkers, John M.; Delaney, Andrew J.

In: Journal of Neuroscience, Vol. 21, No. 17, 01.09.2001, p. 6553-6560.

Research output: Contribution to journalArticle

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