Effects of chronic ethanol treatment on γ-aminobutyric acid(A) and glycine receptors in mouse glycinergic spinal neurons

Brigitte Van Zundert, Felipe A. Albarran, Luis G. Aguayo

Resultado de la investigación: Article

12 Citas (Scopus)

Resumen

Five-day-old cultures of mouse glycinergic spinal interneurons were chronically treated with 100 mM ethanol and the glycine and γ-aminobutyric acid (GABA)(A) receptors were assayed using whole-cell recordings and fluorescence-imaging techniques. Control neurons displayed a glycine50 of 19 ± 0.6 μM and a Hill coefficient of 3.1 ± 0.3. Chronic ethanol treatment did not significantly change these parameters. The maximal responses were 310 ± 80 pA/pF in control and 440 ± 19 pA/pF in treated cells, and the fluorescence intensity associated to a monoclonal glycine receptor antibody was unchanged. Strychnine inhibited the glycine current with smaller potency (29%) in treated neurons, thus the IC50 increased from 14 ± 2 nM in control to 18 ± 6 nM in treated neurons. Zn2+ (10 μM) potentiated the glycine current by 43 ± 33% in control, but only by 18 ± 13% in treated neurons. Interestingly, no change on the inhibition produced by a high concentration of Zn2+ was found in treated neurons. The inhibitory effect of picrotoxin on the glycine receptor, associated to a homomeric receptor, was eliminated with chronic ethanol, suggesting a faster switch to β-subunit-containing receptors. Unlike glycine receptors, the sensitivity of GABA(A) receptors to GABA, pentobarbital, diazepam, and Zn2+, as well as the fluorescence intensity associated to a high-affinity benzodiazepine analog was unchanged by chronic ethanol. In conclusion, we found that glycine receptors in spinal interneurons were altered by chronic ethanol treatment and this may reflect the expression of different subunits in control and treated neurons. GABA(A) receptors were resistant to the treatment.

Idioma originalEnglish
Páginas (desde-hasta)423-429
Número de páginas7
PublicaciónJournal of Pharmacology and Experimental Therapeutics
Volumen295
N.º1
EstadoPublished - 2000

Huella dactilar

Aminobutyrates
Glycine Receptors
Ethanol
Glycine
Neurons
Interneurons
Fluorescence
Strychnine
Picrotoxin
Optical Imaging
Patch-Clamp Techniques
Pentobarbital
Diazepam
Benzodiazepines
Inhibitory Concentration 50
Antibodies

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Citar esto

@article{db84b2b92fe948d288b2f7fc62cc0ec4,
title = "Effects of chronic ethanol treatment on γ-aminobutyric acid(A) and glycine receptors in mouse glycinergic spinal neurons",
abstract = "Five-day-old cultures of mouse glycinergic spinal interneurons were chronically treated with 100 mM ethanol and the glycine and γ-aminobutyric acid (GABA)(A) receptors were assayed using whole-cell recordings and fluorescence-imaging techniques. Control neurons displayed a glycine50 of 19 ± 0.6 μM and a Hill coefficient of 3.1 ± 0.3. Chronic ethanol treatment did not significantly change these parameters. The maximal responses were 310 ± 80 pA/pF in control and 440 ± 19 pA/pF in treated cells, and the fluorescence intensity associated to a monoclonal glycine receptor antibody was unchanged. Strychnine inhibited the glycine current with smaller potency (29{\%}) in treated neurons, thus the IC50 increased from 14 ± 2 nM in control to 18 ± 6 nM in treated neurons. Zn2+ (10 μM) potentiated the glycine current by 43 ± 33{\%} in control, but only by 18 ± 13{\%} in treated neurons. Interestingly, no change on the inhibition produced by a high concentration of Zn2+ was found in treated neurons. The inhibitory effect of picrotoxin on the glycine receptor, associated to a homomeric receptor, was eliminated with chronic ethanol, suggesting a faster switch to β-subunit-containing receptors. Unlike glycine receptors, the sensitivity of GABA(A) receptors to GABA, pentobarbital, diazepam, and Zn2+, as well as the fluorescence intensity associated to a high-affinity benzodiazepine analog was unchanged by chronic ethanol. In conclusion, we found that glycine receptors in spinal interneurons were altered by chronic ethanol treatment and this may reflect the expression of different subunits in control and treated neurons. GABA(A) receptors were resistant to the treatment.",
author = "{Van Zundert}, Brigitte and Albarran, {Felipe A.} and Aguayo, {Luis G.}",
year = "2000",
language = "English",
volume = "295",
pages = "423--429",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

TY - JOUR

T1 - Effects of chronic ethanol treatment on γ-aminobutyric acid(A) and glycine receptors in mouse glycinergic spinal neurons

AU - Van Zundert, Brigitte

AU - Albarran, Felipe A.

AU - Aguayo, Luis G.

PY - 2000

Y1 - 2000

N2 - Five-day-old cultures of mouse glycinergic spinal interneurons were chronically treated with 100 mM ethanol and the glycine and γ-aminobutyric acid (GABA)(A) receptors were assayed using whole-cell recordings and fluorescence-imaging techniques. Control neurons displayed a glycine50 of 19 ± 0.6 μM and a Hill coefficient of 3.1 ± 0.3. Chronic ethanol treatment did not significantly change these parameters. The maximal responses were 310 ± 80 pA/pF in control and 440 ± 19 pA/pF in treated cells, and the fluorescence intensity associated to a monoclonal glycine receptor antibody was unchanged. Strychnine inhibited the glycine current with smaller potency (29%) in treated neurons, thus the IC50 increased from 14 ± 2 nM in control to 18 ± 6 nM in treated neurons. Zn2+ (10 μM) potentiated the glycine current by 43 ± 33% in control, but only by 18 ± 13% in treated neurons. Interestingly, no change on the inhibition produced by a high concentration of Zn2+ was found in treated neurons. The inhibitory effect of picrotoxin on the glycine receptor, associated to a homomeric receptor, was eliminated with chronic ethanol, suggesting a faster switch to β-subunit-containing receptors. Unlike glycine receptors, the sensitivity of GABA(A) receptors to GABA, pentobarbital, diazepam, and Zn2+, as well as the fluorescence intensity associated to a high-affinity benzodiazepine analog was unchanged by chronic ethanol. In conclusion, we found that glycine receptors in spinal interneurons were altered by chronic ethanol treatment and this may reflect the expression of different subunits in control and treated neurons. GABA(A) receptors were resistant to the treatment.

AB - Five-day-old cultures of mouse glycinergic spinal interneurons were chronically treated with 100 mM ethanol and the glycine and γ-aminobutyric acid (GABA)(A) receptors were assayed using whole-cell recordings and fluorescence-imaging techniques. Control neurons displayed a glycine50 of 19 ± 0.6 μM and a Hill coefficient of 3.1 ± 0.3. Chronic ethanol treatment did not significantly change these parameters. The maximal responses were 310 ± 80 pA/pF in control and 440 ± 19 pA/pF in treated cells, and the fluorescence intensity associated to a monoclonal glycine receptor antibody was unchanged. Strychnine inhibited the glycine current with smaller potency (29%) in treated neurons, thus the IC50 increased from 14 ± 2 nM in control to 18 ± 6 nM in treated neurons. Zn2+ (10 μM) potentiated the glycine current by 43 ± 33% in control, but only by 18 ± 13% in treated neurons. Interestingly, no change on the inhibition produced by a high concentration of Zn2+ was found in treated neurons. The inhibitory effect of picrotoxin on the glycine receptor, associated to a homomeric receptor, was eliminated with chronic ethanol, suggesting a faster switch to β-subunit-containing receptors. Unlike glycine receptors, the sensitivity of GABA(A) receptors to GABA, pentobarbital, diazepam, and Zn2+, as well as the fluorescence intensity associated to a high-affinity benzodiazepine analog was unchanged by chronic ethanol. In conclusion, we found that glycine receptors in spinal interneurons were altered by chronic ethanol treatment and this may reflect the expression of different subunits in control and treated neurons. GABA(A) receptors were resistant to the treatment.

UR - http://www.scopus.com/inward/record.url?scp=0033803404&partnerID=8YFLogxK

M3 - Article

C2 - 10992010

AN - SCOPUS:0033803404

VL - 295

SP - 423

EP - 429

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 1

ER -