Arachidonic acid activates an open rectifier potassium channel in cultured rat cortical astrocytes

Autor: Pierluigi Valente, Peter Schubert, Marco Caprini, Mario Nobile, Carmela Rapisarda, Stefano Ferroni
Rok vydání: 2003
Předmět:
Quinidine
Epoxygenase
medicine.medical_specialty
Patch-Clamp Techniques
Potassium Channels
Membrane Potentials
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Potassium Channels
Tandem Pore Domain
Animals
Arachidonic Acid
pharmacology
Astrocytes
cytology/drug effects/metabolism
Cerebral Cortex
cytology/drug effects/metabolism
Drosophila Proteins
Enzyme Inhibitors
pharmacology
Membrane Potentials
drug effects
Patch-Clamp Techniques
Potassium Channel Blockers
pharmacology
Potassium Channels
Tandem Pore Domain
Potassium Channels
drug effects/metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
drug effects/physiology
Internal medicine
medicine
Potassium Channel Blockers
Animals
Drosophila Proteins
Patch clamp
Enzyme Inhibitors
Tandem Pore Domain
Protein kinase C
Membrane potential
Cerebral Cortex
Tetraethylammonium
Arachidonic Acid
biology
Chemistry
Reverse Transcriptase Polymerase Chain Reaction
Potassium channel blocker
cytology/drug effects/metabolism
Potassium channel
Rats
Endocrinology
drug effects
Astrocytes
biology.protein
Biophysics
pharmacology
drug effects/metabolism
medicine.drug
Signal Transduction
Zdroj: Journal of neuroscience research 72 (2003): 363–372.
info:cnr-pdr/source/autori:Ferroni S., Valente P., Caprini M., Nobile M., Schubert P., Rapisarda C./titolo:Arachidonic acid activates an open rectifier potassium channel in cultured rat cortical astrocytes./doi:/rivista:Journal of neuroscience research/anno:2003/pagina_da:363/pagina_a:372/intervallo_pagine:363–372/volume:72
ISSN: 0360-4012
Popis: A pathophysiological increase in free arachidonic acid (AA) is thought to regulate the channel-mediated astrocytic swelling occurring in several brain injuries. We report that in cultured rat type-1 cortical astrocytes, exposure to 10 microM AA activates an open rectifier K(+) channel, which exhibits many similarities with TREK/TRAAK members of the two-pore-domain K(+) channel family KCNK. Patch-clamp experiments showed that the current developed with a long latency and was preceded by a depression of the previously described outward rectifier K(+) conductance. Pharmacologic studies indicate that the K(+) open rectifier was differentially sensitive to classic K(+)-channel blockers (quinine, quinidine, tetraethylammonium, and barium) and was inhibited potently by gadolinium ions. The activation of this K(+) current occurred independently of the AA metabolism as pharmacologic inhibition of the lipoxygenase, cyclooxygenase, and cytochrome P450 epoxygenase signaling cascades did not alter the AA effect. Moreover, neither the neutralization of the NADPH-oxidase pathway nor scavenging intracellular free radicals modified the AA response. Finally, the AA-induced K(+) current was unaffected by protein kinase C inhibitors. The activation mechanism of the K(+) open rectifier was through an extracellular interaction of AA with the plasma membrane. RT-PCR analysis revealed that the AA-induced K(+) conductance was mediated likely by TREK-2 channels. Collectively, the results demonstrate that in cultured cortical astrocytes, pathological levels of AA directly activate an open rectifier K(+) channel, which may play a role in the control of K(+) homeostasis under pathophysiological conditions.
Databáze: OpenAIRE
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