Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.

Cerebellar granule cells (CGNs) are one of many neurons that express phasic and tonic GABAergic conductances. Although it is well established that Golgi cells (GoCs) mediate phasic GABAergic currents in CGNs, their role in mediating tonic currents in CGNs (CGN-I(tonic)) is controversial. Earlier stu...

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Autores principales: Marvin R Diaz, Aya Wadleigh, Shyam Kumar, Erik De Schutter, C Fernando Valenzuela
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:6fb3af42b9024b24be061c163a30490d2021-11-18T07:59:05ZNa+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.1932-620310.1371/journal.pone.0055673https://doaj.org/article/6fb3af42b9024b24be061c163a30490d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23383260/?tool=EBIhttps://doaj.org/toc/1932-6203Cerebellar granule cells (CGNs) are one of many neurons that express phasic and tonic GABAergic conductances. Although it is well established that Golgi cells (GoCs) mediate phasic GABAergic currents in CGNs, their role in mediating tonic currents in CGNs (CGN-I(tonic)) is controversial. Earlier studies suggested that GoCs mediate a component of CGN-I(tonic) that is present only in preparations from immature rodents. However, more recent studies have detected a GoC-dependent component of CGN-I(tonic) in preparations of mature rodents. In addition, acute exposure to ethanol was shown to potentiate the GoC component of CGN-I(tonic) and to induce a parallel increase in spontaneous inhibitory postsynaptic current frequency at CGNs. Here, we tested the hypothesis that these effects of ethanol on GABAergic transmission in CGNs are mediated by inhibition of the Na(+)/K(+)-ATPase. We used whole-cell patch-clamp electrophysiology techniques in cerebellar slices of male rats (postnatal day 23-30). Under these conditions, we reliably detected a GoC-dependent component of CGN-I(tonic) that could be blocked with tetrodotoxin. Further analysis revealed a positive correlation between basal sIPSC frequency and the magnitude of the GoC-dependent component of CGN-I(tonic). Inhibition of the Na(+)/K(+)-ATPase with a submaximal concentration of ouabain partially mimicked the ethanol-induced potentiation of both phasic and tonic GABAergic currents in CGNs. Modeling studies suggest that selective inhibition of the Na(+)/K(+)-ATPase in GoCs can, in part, explain these effects of ethanol. These findings establish a novel mechanism of action of ethanol on GABAergic transmission in the central nervous system.Marvin R DiazAya WadleighShyam KumarErik De SchutterC Fernando ValenzuelaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e55673 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Marvin R Diaz
Aya Wadleigh
Shyam Kumar
Erik De Schutter
C Fernando Valenzuela
Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.
description Cerebellar granule cells (CGNs) are one of many neurons that express phasic and tonic GABAergic conductances. Although it is well established that Golgi cells (GoCs) mediate phasic GABAergic currents in CGNs, their role in mediating tonic currents in CGNs (CGN-I(tonic)) is controversial. Earlier studies suggested that GoCs mediate a component of CGN-I(tonic) that is present only in preparations from immature rodents. However, more recent studies have detected a GoC-dependent component of CGN-I(tonic) in preparations of mature rodents. In addition, acute exposure to ethanol was shown to potentiate the GoC component of CGN-I(tonic) and to induce a parallel increase in spontaneous inhibitory postsynaptic current frequency at CGNs. Here, we tested the hypothesis that these effects of ethanol on GABAergic transmission in CGNs are mediated by inhibition of the Na(+)/K(+)-ATPase. We used whole-cell patch-clamp electrophysiology techniques in cerebellar slices of male rats (postnatal day 23-30). Under these conditions, we reliably detected a GoC-dependent component of CGN-I(tonic) that could be blocked with tetrodotoxin. Further analysis revealed a positive correlation between basal sIPSC frequency and the magnitude of the GoC-dependent component of CGN-I(tonic). Inhibition of the Na(+)/K(+)-ATPase with a submaximal concentration of ouabain partially mimicked the ethanol-induced potentiation of both phasic and tonic GABAergic currents in CGNs. Modeling studies suggest that selective inhibition of the Na(+)/K(+)-ATPase in GoCs can, in part, explain these effects of ethanol. These findings establish a novel mechanism of action of ethanol on GABAergic transmission in the central nervous system.
format article
author Marvin R Diaz
Aya Wadleigh
Shyam Kumar
Erik De Schutter
C Fernando Valenzuela
author_facet Marvin R Diaz
Aya Wadleigh
Shyam Kumar
Erik De Schutter
C Fernando Valenzuela
author_sort Marvin R Diaz
title Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.
title_short Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.
title_full Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.
title_fullStr Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.
title_full_unstemmed Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.
title_sort na+/k+-atpase inhibition partially mimics the ethanol-induced increase of the golgi cell-dependent component of the tonic gabaergic current in rat cerebellar granule cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/6fb3af42b9024b24be061c163a30490d
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