Pharmacological upregulation of h-channels reduces the excitability of pyramidal neuron dendrites

The dendrites of pyramidal neurons have markedly different electrical properties from those of the soma, owing to the non-uniform distribution of voltage-gated ion channels in dendrites. It is thus possible that drugs acting on ion channels might preferentially alter dendritic, but not somatic, exci...

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Veröffentlicht in:Nature neuroscience 2002-08, Vol.5 (8), p.767-774
Hauptverfasser: Johnston, Daniel, Poolos, Nicholas P, Migliore, Michele
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Poolos, Nicholas P
Migliore, Michele
description The dendrites of pyramidal neurons have markedly different electrical properties from those of the soma, owing to the non-uniform distribution of voltage-gated ion channels in dendrites. It is thus possible that drugs acting on ion channels might preferentially alter dendritic, but not somatic, excitability. Using dendritic and somatic whole-cell and cell-attached recordings in rat hippocampal slices, we found that the anticonvulsant lamotrigine selectively reduced action potential firing from dendritic depolarization, while minimally affecting firing at the soma. This regional and input-specific effect resulted from an increase in the hyperpolarization-activated cation current ( I h ), a voltage-gated current present predominantly in dendrites. These results demonstrate that neuronal excitability can be altered by drugs acting selectively on dendrites, and suggest an important role for I h in controlling dendritic excitability and epileptogenesis.
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subjects Action Potentials - drug effects
Action Potentials - physiology
Animal Genetics and Genomics
Animals
Behavioral Sciences
Biological Techniques
Biomedical and Life Sciences
Biomedicine
Calcium Channel Blockers - pharmacology
Cyclic Nucleotide-Gated Cation Channels
Dendrites
Dendrites - drug effects
Dendrites - physiology
Electric Stimulation
Excitatory Amino Acid Antagonists - pharmacology
Excitatory Postsynaptic Potentials - physiology
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - metabolism
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
In Vitro Techniques
Ion channels
Ion Channels - drug effects
Ion Channels - metabolism
Male
Models, Neurological
Neurobiology
Neurosciences
Patch-Clamp Techniques
Physiological aspects
Potassium Channels
Pyramidal Cells - cytology
Pyramidal Cells - drug effects
Pyramidal Cells - metabolism
Rats
Rats, Sprague-Dawley
Triazines - pharmacology
Up-Regulation - drug effects
Up-Regulation - physiology
title Pharmacological upregulation of h-channels reduces the excitability of pyramidal neuron dendrites
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