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PMID: 11404400 Published · ppublish English Journal Article

Kinetic modulation of Kv4-mediated A-current by arachidonic acid is dependent on potassium channel interacting proteins.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 12 ·2001-06-15 ·Pages 4154-61

Holmqvist MH, Cao J, Knoppers MH, Jurman ME, Distefano PS, Rhodes KJ, Xie Y, An WF

Abstract

The Kv4 subfamily of voltage-gated potassium channels is responsible for the transient A-type potassium current that operates at subthreshold membrane potentials to control membrane excitability. Arachidonic acid was shown recently to modulate both the peak amplitude and kinetics of the hippocampal A-current. However, in Xenopus oocytes, arachidonic acid only inhibited the peak amplitude of Kv4 current without modifying its kinetics. These results suggest the existence of Kv4 auxiliary subunit(s) in native cells. We report here a K-channel interacting protein (KChIP)-dependent kinetic modulation of Kv4.2 current in Chinese hamster ovary cells and Kv4.2 and Kv4.3 currents in Xenopus oocytes by arachidonic acid at physiological concentrations. This concentration-dependent effect of arachidonic acid resembled that observed in cerebellar granule neurons and was fully reversible. Other fatty acids, including a nonhydrolyzable inhibitor of both lipooxygenase and cyclooxygenase, 5,8,11,14-eicosatetraynoic acid (ETYA), also mimicked arachidonic acid in modulating Kv4.3 and Kv4.3/KChIP1 currents. Compared with another transient potassium current formed by Kv1.1/Kvbeta1, Kv4.3/KChIP1 current was much more sensitive to arachidonic acid. Association between KChIP1 and Kv4.2 or Kv4.3 was not altered in the presence of 10 microm ETYA as measured by immunoprecipitation and association-dependent growth in yeast. Our data suggest that the KChIP proteins represent a molecular entity for the observed difference between arachidonic acid effects on A-current kinetics in heterologous cells and in native cells and are consistent with the notion that KChIP proteins modulate the subthreshold A-current in neurons.

MeSH Terms
5,8,11,14-Eicosatetraynoic Acid/pharmacology Animals Arachidonic Acid/pharmacology CHO Cells Calcium-Binding Proteins/genetics,metabolism Cells, Cultured Cricetinae Dose-Response Relationship, Drug Fatty Acids/pharmacology Humans Kv Channel-Interacting Proteins Membrane Potentials/drug effects,physiology Neurons/cytology,drug effects,metabolism Oocytes/metabolism Patch-Clamp Techniques Potassium/metabolism Potassium Channels/genetics,metabolism Potassium Channels, Voltage-Gated Protein Binding/drug effects Protein Subunits Rats Rats, Sprague-Dawley Shal Potassium Channels Transfection Two-Hybrid System Techniques Xenopus laevis
Chemicals
Calcium-Binding Proteins Fatty Acids KCND2 protein, human KCND3 protein, human KCNIP1 protein, human Kcnd2 protein, rat Kcnd3 protein, rat Kcnip1 protein, rat Kv Channel-Interacting Proteins Potassium Channels Potassium Channels, Voltage-Gated Protein Subunits Shal Potassium Channels 5,8,11,14-Eicosatetraynoic Acid Arachidonic Acid Potassium
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Holmqvist M H
Millennium Pharmaceuticals Inc., Cambridge, Massachusetts 02139, USA.
Cao J
Knoppers M H
Jurman M E
Distefano P S
Rhodes K J
Xie Y
An W F
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-06-15
Pages
4154-61
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762757
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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