title: Arachidonic acid activates an open rectifier potassium channel in cultured rat cortical astrocytes.
abstract: 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.
authors.affiliation: Department of Human and General Physiology, University of Bologna, Bologna, Italy. ferroni@biofarm.unibo.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferroni
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Valente
authors.forename: Marco
authors.initials: M
authors.lastname: Caprini
authors.forename: Mario
authors.initials: M
authors.lastname: Nobile
authors.forename: Peter
authors.initials: P
authors.lastname: Schubert
authors.forename: Carmela
authors.initials: C
authors.lastname: Rapisarda
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; C503444:Kcnk10 protein, rat; C102352:Ork1 protein, Drosophila; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D016718:Arachidonic Acid