K-Cl Cotransporter 2–mediated Cl− Extrusion Determines Developmental Stage–dependent Impact of Propofol Anesthesia on Dendritic Spines

Handle URI:
http://hdl.handle.net/10754/623859
Title:
K-Cl Cotransporter 2–mediated Cl− Extrusion Determines Developmental Stage–dependent Impact of Propofol Anesthesia on Dendritic Spines
Authors:
Puskarjov, Martin; Fiumelli, Hubert ( 0000-0001-5136-3045 ) ; Briner, Adrian; Bodogan, Timea; Demeter, Kornel; Lacoh, Claudia Marvine; Mavrovic, Martina; Blaesse, Peter; Kaila, Kai; Vutskits, Laszlo
Abstract:
Background: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABA A)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2). Methods: In utero electroporation of KCC2 was used to prematurely increase the efficacy of (GABA A)-mediated inhibition in layer 2/3 pyramidal neurons in the immature rat somatosensory cortex. Parallel experiments with expression of the inward-rectifier potassium channel Kir2.1 were done to reduce intrinsic neuronal excitability. The effects of these genetic manipulations (n = 3 to 4 animals per experimental group) were evaluated using iontophoretic injection of Lucifer Yellow (n = 8 to 12 cells per animal). The total number of spines analyzed per group ranged between 907 and 3,371. Results: The authors found a robust effect of the developmental up-regulation of KCC2-mediated Cl - transport on the age-dependent action of propofol on dendritic spines. Premature expression of KCC2, unlike expression of a transport-inactive KCC2 variant, prevented a propofol-induced decrease in spine density. In line with a reduction in neuronal excitability, the above result was qualitatively replicated by overexpression of Kir2.1. Conclusions: The KCC2-dependent developmental increase in the efficacy of GABA A -mediated inhibition is a major determinant of the age-dependent actions of propofol on dendritic spinogenesis.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Puskarjov M, Fiumelli H, Briner A, Bodogan T, Demeter K, et al. (2017) K-Cl Cotransporter 2–mediated Cl− Extrusion Determines Developmental Stage–dependent Impact of Propofol Anesthesia on Dendritic Spines. Anesthesiology 126: 855–867. Available: http://dx.doi.org/10.1097/ALN.0000000000001587.
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Journal:
Anesthesiology
Issue Date:
16-Mar-2017
DOI:
10.1097/ALN.0000000000001587
Type:
Article
ISSN:
0003-3022
Additional Links:
http://insights.ovid.com/crossref?an=00000542-201705000-00022
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorPuskarjov, Martinen
dc.contributor.authorFiumelli, Huberten
dc.contributor.authorBriner, Adrianen
dc.contributor.authorBodogan, Timeaen
dc.contributor.authorDemeter, Kornelen
dc.contributor.authorLacoh, Claudia Marvineen
dc.contributor.authorMavrovic, Martinaen
dc.contributor.authorBlaesse, Peteren
dc.contributor.authorKaila, Kaien
dc.contributor.authorVutskits, Laszloen
dc.date.accessioned2017-05-31T11:23:10Z-
dc.date.available2017-05-31T11:23:10Z-
dc.date.issued2017-03-16en
dc.identifier.citationPuskarjov M, Fiumelli H, Briner A, Bodogan T, Demeter K, et al. (2017) K-Cl Cotransporter 2–mediated Cl− Extrusion Determines Developmental Stage–dependent Impact of Propofol Anesthesia on Dendritic Spines. Anesthesiology 126: 855–867. Available: http://dx.doi.org/10.1097/ALN.0000000000001587.en
dc.identifier.issn0003-3022en
dc.identifier.doi10.1097/ALN.0000000000001587en
dc.identifier.urihttp://hdl.handle.net/10754/623859-
dc.description.abstractBackground: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABA A)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2). Methods: In utero electroporation of KCC2 was used to prematurely increase the efficacy of (GABA A)-mediated inhibition in layer 2/3 pyramidal neurons in the immature rat somatosensory cortex. Parallel experiments with expression of the inward-rectifier potassium channel Kir2.1 were done to reduce intrinsic neuronal excitability. The effects of these genetic manipulations (n = 3 to 4 animals per experimental group) were evaluated using iontophoretic injection of Lucifer Yellow (n = 8 to 12 cells per animal). The total number of spines analyzed per group ranged between 907 and 3,371. Results: The authors found a robust effect of the developmental up-regulation of KCC2-mediated Cl - transport on the age-dependent action of propofol on dendritic spines. Premature expression of KCC2, unlike expression of a transport-inactive KCC2 variant, prevented a propofol-induced decrease in spine density. In line with a reduction in neuronal excitability, the above result was qualitatively replicated by overexpression of Kir2.1. Conclusions: The KCC2-dependent developmental increase in the efficacy of GABA A -mediated inhibition is a major determinant of the age-dependent actions of propofol on dendritic spinogenesis.en
dc.publisherOvid Technologies (Wolters Kluwer Health)en
dc.relation.urlhttp://insights.ovid.com/crossref?an=00000542-201705000-00022en
dc.titleK-Cl Cotransporter 2–mediated Cl− Extrusion Determines Developmental Stage–dependent Impact of Propofol Anesthesia on Dendritic Spinesen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalAnesthesiologyen
dc.contributor.institutionDepartment of Biosciences and Neuroscience Center (HiLIFE), University of Helsinki, Helsinki, , Finlanden
dc.contributor.institutionDepartment of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, 4, Rue Gabrielle-Perret-Gentil, Geneva 4, 1211, , Switzerlanden
dc.contributor.institutionDepartment of Fundamental Neurosciences, University of Geneva Medical School, Geneva, , Switzerlanden
dc.contributor.institutionInstitute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, , , Hungaryen
dc.contributor.institutionInstitute of Physiology i, Westfälische Wilhelms-University Münster, Münster, , Germanyen
kaust.authorFiumelli, Huberten
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