A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures. / Suñol, C; Babot, Z; Cristòfol, R; Sonnewald, U; Waagepetersen, Helle S.; Schousboe, A.

I: Neurochemical Research, Bind 35, Nr. 9, 09.2010, s. 1384-1390.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Suñol, C, Babot, Z, Cristòfol, R, Sonnewald, U, Waagepetersen, HS & Schousboe, A 2010, 'A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures', Neurochemical Research, bind 35, nr. 9, s. 1384-1390. https://doi.org/10.1007/s11064-010-0196-1

APA

Suñol, C., Babot, Z., Cristòfol, R., Sonnewald, U., Waagepetersen, H. S., & Schousboe, A. (2010). A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures. Neurochemical Research, 35(9), 1384-1390. https://doi.org/10.1007/s11064-010-0196-1

Vancouver

Suñol C, Babot Z, Cristòfol R, Sonnewald U, Waagepetersen HS, Schousboe A. A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures. Neurochemical Research. 2010 sep.;35(9):1384-1390. https://doi.org/10.1007/s11064-010-0196-1

Author

Suñol, C ; Babot, Z ; Cristòfol, R ; Sonnewald, U ; Waagepetersen, Helle S. ; Schousboe, A. / A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures. I: Neurochemical Research. 2010 ; Bind 35, Nr. 9. s. 1384-1390.

Bibtex

@article{537590db6d18478d8e42177ee97c6ad8,
title = "A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures",
abstract = "Cultures of dissociated cerebellum from 7-day-old mice were used to investigate the mechanism involved in synthesis and cellular redistribution of GABA in these cultures consisting primarily of glutamatergic granule neurons and a smaller population of GABAergic Golgi and stellate neurons. The distribution of GAD, GABA and the vesicular glutamate transporter VGlut-1 was assessed using specific antibodies combined with immunofluorescence microscopy. Additionally, tiagabine, SKF 89976-A, betaine, beta-alanine, nipecotic acid and guvacine were used to inhibit the GAT1, betaine/GABA (BGT1), GAT2 and GAT3 transporters. Only a small population of cells were immuno-stained for GAD while many cells exhibited VGlut-1 like immuno-reactivity which, however, never co-localized with GAD positive neurons. This likely reflects the small number of GABAergic neurons compared to the glutamatergic granule neurons constituting the majority of the cells. GABA uptake exhibited the kinetics of high affinity transport and could be partly (20%) inhibited by betaine (IC(50) 142 microM), beta-alanine (30%) and almost fully (90%) inhibited by SKF 89976-A (IC(50) 0.8 microM) or nipecotic acid and guvacine at 1 mM concentrations (95%). Essentially all neurons showed GABA like immunostaining albeit with differences in intensity. The results indicate that GABA which is synthesized in a small population of GAD-positive neurons is redistributed to essentially all neurons including the glutamatergic granule cells. GAT1 is not likely involved in this redistribution since addition of 15 microM tiagabine (GAT1 inhibitor) to the culture medium had no effect on the overall GABA content of the cells. Likewise the BGT1 transporter cannot alone account for the redistribution since inclusion of 3 mM betaine in the culture medium had no effect on the overall GABA content. The inhibitory action of beta-alanine and high concentrations of nipecotic acid and guvacine on GABA transport strongly suggests that also GAT2 or GAT3 (HUGO nomenclature) could play a role.",
keywords = "Former Faculty of Pharmaceutical Sciences, GABA, Transport, Cerebellar granule neurons, BGT1, GAT2, GAT3",
author = "C Su{\~n}ol and Z Babot and R Crist{\`o}fol and U Sonnewald and Waagepetersen, {Helle S.} and A Schousboe",
year = "2010",
month = sep,
doi = "10.1007/s11064-010-0196-1",
language = "English",
volume = "35",
pages = "1384--1390",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer",
number = "9",

}

RIS

TY - JOUR

T1 - A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures

AU - Suñol, C

AU - Babot, Z

AU - Cristòfol, R

AU - Sonnewald, U

AU - Waagepetersen, Helle S.

AU - Schousboe, A

PY - 2010/9

Y1 - 2010/9

N2 - Cultures of dissociated cerebellum from 7-day-old mice were used to investigate the mechanism involved in synthesis and cellular redistribution of GABA in these cultures consisting primarily of glutamatergic granule neurons and a smaller population of GABAergic Golgi and stellate neurons. The distribution of GAD, GABA and the vesicular glutamate transporter VGlut-1 was assessed using specific antibodies combined with immunofluorescence microscopy. Additionally, tiagabine, SKF 89976-A, betaine, beta-alanine, nipecotic acid and guvacine were used to inhibit the GAT1, betaine/GABA (BGT1), GAT2 and GAT3 transporters. Only a small population of cells were immuno-stained for GAD while many cells exhibited VGlut-1 like immuno-reactivity which, however, never co-localized with GAD positive neurons. This likely reflects the small number of GABAergic neurons compared to the glutamatergic granule neurons constituting the majority of the cells. GABA uptake exhibited the kinetics of high affinity transport and could be partly (20%) inhibited by betaine (IC(50) 142 microM), beta-alanine (30%) and almost fully (90%) inhibited by SKF 89976-A (IC(50) 0.8 microM) or nipecotic acid and guvacine at 1 mM concentrations (95%). Essentially all neurons showed GABA like immunostaining albeit with differences in intensity. The results indicate that GABA which is synthesized in a small population of GAD-positive neurons is redistributed to essentially all neurons including the glutamatergic granule cells. GAT1 is not likely involved in this redistribution since addition of 15 microM tiagabine (GAT1 inhibitor) to the culture medium had no effect on the overall GABA content of the cells. Likewise the BGT1 transporter cannot alone account for the redistribution since inclusion of 3 mM betaine in the culture medium had no effect on the overall GABA content. The inhibitory action of beta-alanine and high concentrations of nipecotic acid and guvacine on GABA transport strongly suggests that also GAT2 or GAT3 (HUGO nomenclature) could play a role.

AB - Cultures of dissociated cerebellum from 7-day-old mice were used to investigate the mechanism involved in synthesis and cellular redistribution of GABA in these cultures consisting primarily of glutamatergic granule neurons and a smaller population of GABAergic Golgi and stellate neurons. The distribution of GAD, GABA and the vesicular glutamate transporter VGlut-1 was assessed using specific antibodies combined with immunofluorescence microscopy. Additionally, tiagabine, SKF 89976-A, betaine, beta-alanine, nipecotic acid and guvacine were used to inhibit the GAT1, betaine/GABA (BGT1), GAT2 and GAT3 transporters. Only a small population of cells were immuno-stained for GAD while many cells exhibited VGlut-1 like immuno-reactivity which, however, never co-localized with GAD positive neurons. This likely reflects the small number of GABAergic neurons compared to the glutamatergic granule neurons constituting the majority of the cells. GABA uptake exhibited the kinetics of high affinity transport and could be partly (20%) inhibited by betaine (IC(50) 142 microM), beta-alanine (30%) and almost fully (90%) inhibited by SKF 89976-A (IC(50) 0.8 microM) or nipecotic acid and guvacine at 1 mM concentrations (95%). Essentially all neurons showed GABA like immunostaining albeit with differences in intensity. The results indicate that GABA which is synthesized in a small population of GAD-positive neurons is redistributed to essentially all neurons including the glutamatergic granule cells. GAT1 is not likely involved in this redistribution since addition of 15 microM tiagabine (GAT1 inhibitor) to the culture medium had no effect on the overall GABA content of the cells. Likewise the BGT1 transporter cannot alone account for the redistribution since inclusion of 3 mM betaine in the culture medium had no effect on the overall GABA content. The inhibitory action of beta-alanine and high concentrations of nipecotic acid and guvacine on GABA transport strongly suggests that also GAT2 or GAT3 (HUGO nomenclature) could play a role.

KW - Former Faculty of Pharmaceutical Sciences

KW - GABA

KW - Transport

KW - Cerebellar granule neurons

KW - BGT1

KW - GAT2

KW - GAT3

U2 - 10.1007/s11064-010-0196-1

DO - 10.1007/s11064-010-0196-1

M3 - Journal article

C2 - 20512624

VL - 35

SP - 1384

EP - 1390

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 9

ER -

ID: 34206186