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Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes.
- Source :
-
Endocrinology [Endocrinology] 2011 May; Vol. 152 (5), pp. 1901-10. Date of Electronic Publication: 2011 Feb 22. - Publication Year :
- 2011
-
Abstract
- Arachidonic acid (AA) is generated in the anterior pituitary gland upon stimulation by the ACTH secretagogue, CRH. Using the patch clamp technique, we examined the action of AA on the excitability of single pituitary corticotropes obtained from a transgenic mouse strain that expresses the enhanced green fluorescent protein driven by the proopiomelanocortin promoter. CRH evoked depolarization, but AA caused hyperpolarization. Under voltage clamp condition, AA caused a rapid inhibition of the delayed rectifier K(+) current and then increased a background K(+) current. Inhibition of AA metabolism did not prevent the activation of the K(+) current by AA, suggesting a direct action of AA. The sensitivity of the AA-activated K(+) current to fluoxetine, chlorpromazine, extracellular acidification, diphenylbutylpiperidine antipsychotics, and the membrane permeable cAMP analog [8-(4-chlorophenylthio)-cAMP] suggest that the current is mediated via TWIK-related K(+) channel (TREK)-1 channels. Activation of the CRH receptors that are coupled to the adenylate cyclase pathway suppressed the activation of TREK-1 current by AA and reversed the AA-mediated hyperpolarization. Intracellular acidification (pH 7.0) increased the basal amplitude of TREK-1 current and resulted in hyperpolarizaton. CRH suppressed the basal TREK-1 current in cells with intracellular acidification and caused depolarization. Our finding indicates that TREK-1 channels are important in setting the resting potential in corticotropes. The opposing actions of CRH and AA on the excitability of corticotropes raise the possibility that AA may act as a negative feedback regulator to reduce the stimulatory action of CRH and thus prevent excessive ACTH release during chronic stress.
- Subjects :
- Animals
Cells, Cultured
Chlorpromazine pharmacology
Corticotrophs cytology
Corticotrophs metabolism
Cyclic AMP analogs & derivatives
Cyclic AMP pharmacology
Fluoxetine pharmacology
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Hydrogen-Ion Concentration
Membrane Potentials drug effects
Mice
Mice, Transgenic
Neuroprotective Agents pharmacology
Patch-Clamp Techniques
Thionucleotides pharmacology
Arachidonic Acid pharmacology
Corticotrophs physiology
Corticotropin-Releasing Hormone pharmacology
Potassium Channels, Tandem Pore Domain physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 152
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 21343252
- Full Text :
- https://doi.org/10.1210/en.2010-1066