Depolarization-induced release of [(3)H]D-aspartate from GABAergic neurons caused by reversal of glutamate transporters

J B Jensen; D S Pickering; A Schousboe; Darryl Pickering

Depolarization-induced release of [(3)H]D-aspartate from GABAergic neurons caused by reversal of glutamate transporters

J B Jensen, D S Pickering, A Schousboe, Darryl Pickering

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

26 Citationer (Scopus)

Abstract

Udgivelsesdato: null-null

Originalsprog	Engelsk
Tidsskrift	International Journal of Developmental Neuroscience
Vol/bind	18
Udgave nummer	2-3
Sider (fra-til)	309-15
Antal sider	6
ISSN	0736-5748
Status	Udgivet - 2000

Bibliografisk note

Keywords: Animals; Aspartic Acid; Benzothiadiazines; Cells, Cultured; Cerebral Cortex; Diuretics; Excitatory Amino Acid Agonists; Female; Glutamic Acid; Kainic Acid; Mice; Mice, Inbred Strains; Neurons; Potassium; Pregnancy; Receptors, AMPA; Receptors, Kainic Acid; Sodium Chloride Symporter Inhibitors; Tritium; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; gamma-Aminobutyric Acid

Citationsformater

@article{e5e828206e8f11df928f000ea68e967b,

title = "Depolarization-induced release of [(3)H]D-aspartate from GABAergic neurons caused by reversal of glutamate transporters",

abstract = "Cultured neocortical neurons, which predominantly consist of GABAergic neurons exhibit a pronounced stimulus-coupled GABA release. Since the cultures may contain a small population of glutamatergic neurons and the GABAergic neurons have a high content of glutamate it was of interest to examine if glutamate in addition to gamma-aminobutyric acid (GABA) could be released from these cultures. The neurons were preloaded with [(3)H]D-aspartate and subsequently its release was followed during depolarization induced by a high potassium concentration or the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonists, AMPA and kainate. Depolarization of the neurons with 55 mM potassium increased the release of [(3)H]D-aspartate by more than 10-fold. When the non-specific calcium-channel blockers cobalt or lanthanum were included in the stimulation buffer with potassium, the release of [(3)H]D-aspartate was decreased by about 40%. These results indicated that some of the released [(3)H]D-aspartate might originate from a vesicular pool. When AMPA was applied to the neurons, the release of [(3)H]D-aspartate was increased 2-fold and could not be prevented or decreased by addition of cobalt. Since AMPA has a rapid desensitizing effect on AMPA receptors, it was examined whether AMPA under non-desensitizing conditions was able to induce an increased release of [(3)H]D-aspartate as compared to the conditions of applying AMPA alone. The desensitization of AMPA receptors was blocked by 6-chloro-3,4-dihydro-3-(2-norbornen-5-yl)-2H-1,2, 4-benzothiadiazine-7-sulphonamide-1,1-dioxide (cyclothiazide). Under the non-desensitizing conditions, the AMPA-induced release of [(3)H]D-aspartate was highly enhanced showing about a 10-fold increase over basal release. Addition of cobalt or lanthanum did not decrease the amount of [(3)H]D-aspartate released, indicating that the release originated from a cytoplasmic pool. Kainate, which induces an almost non-desensitizing effect on AMPA receptors, showed similar results as observed for AMPA under non-desensitizing conditions. The NMDA receptor antagonist (5R,10 S)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) had only minor effects on the [(3)H]D-aspartate release induced by AMPA and kainate. Thus, the depolarization-induced release of [(3)H]D-aspartate from cultured GABAergic neurons appears to be caused mainly by reversal of the glutamate transporters.",

author = "Jensen, {J B} and Pickering, {D S} and A Schousboe and Darryl Pickering",

note = "Keywords: Animals; Aspartic Acid; Benzothiadiazines; Cells, Cultured; Cerebral Cortex; Diuretics; Excitatory Amino Acid Agonists; Female; Glutamic Acid; Kainic Acid; Mice; Mice, Inbred Strains; Neurons; Potassium; Pregnancy; Receptors, AMPA; Receptors, Kainic Acid; Sodium Chloride Symporter Inhibitors; Tritium; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; gamma-Aminobutyric Acid",

year = "2000",

language = "English",

volume = "18",

pages = "309--15",

journal = "International Journal of Developmental Neuroscience",

issn = "0736-5748",

publisher = "Pergamon Press",

number = "2-3",

}

TY - JOUR

T1 - Depolarization-induced release of [(3)H]D-aspartate from GABAergic neurons caused by reversal of glutamate transporters

AU - Jensen, J B

AU - Pickering, D S

AU - Schousboe, A

AU - Pickering, Darryl

N1 - Keywords: Animals; Aspartic Acid; Benzothiadiazines; Cells, Cultured; Cerebral Cortex; Diuretics; Excitatory Amino Acid Agonists; Female; Glutamic Acid; Kainic Acid; Mice; Mice, Inbred Strains; Neurons; Potassium; Pregnancy; Receptors, AMPA; Receptors, Kainic Acid; Sodium Chloride Symporter Inhibitors; Tritium; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; gamma-Aminobutyric Acid

PY - 2000

Y1 - 2000

N2 - Cultured neocortical neurons, which predominantly consist of GABAergic neurons exhibit a pronounced stimulus-coupled GABA release. Since the cultures may contain a small population of glutamatergic neurons and the GABAergic neurons have a high content of glutamate it was of interest to examine if glutamate in addition to gamma-aminobutyric acid (GABA) could be released from these cultures. The neurons were preloaded with [(3)H]D-aspartate and subsequently its release was followed during depolarization induced by a high potassium concentration or the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonists, AMPA and kainate. Depolarization of the neurons with 55 mM potassium increased the release of [(3)H]D-aspartate by more than 10-fold. When the non-specific calcium-channel blockers cobalt or lanthanum were included in the stimulation buffer with potassium, the release of [(3)H]D-aspartate was decreased by about 40%. These results indicated that some of the released [(3)H]D-aspartate might originate from a vesicular pool. When AMPA was applied to the neurons, the release of [(3)H]D-aspartate was increased 2-fold and could not be prevented or decreased by addition of cobalt. Since AMPA has a rapid desensitizing effect on AMPA receptors, it was examined whether AMPA under non-desensitizing conditions was able to induce an increased release of [(3)H]D-aspartate as compared to the conditions of applying AMPA alone. The desensitization of AMPA receptors was blocked by 6-chloro-3,4-dihydro-3-(2-norbornen-5-yl)-2H-1,2, 4-benzothiadiazine-7-sulphonamide-1,1-dioxide (cyclothiazide). Under the non-desensitizing conditions, the AMPA-induced release of [(3)H]D-aspartate was highly enhanced showing about a 10-fold increase over basal release. Addition of cobalt or lanthanum did not decrease the amount of [(3)H]D-aspartate released, indicating that the release originated from a cytoplasmic pool. Kainate, which induces an almost non-desensitizing effect on AMPA receptors, showed similar results as observed for AMPA under non-desensitizing conditions. The NMDA receptor antagonist (5R,10 S)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) had only minor effects on the [(3)H]D-aspartate release induced by AMPA and kainate. Thus, the depolarization-induced release of [(3)H]D-aspartate from cultured GABAergic neurons appears to be caused mainly by reversal of the glutamate transporters.

AB - Cultured neocortical neurons, which predominantly consist of GABAergic neurons exhibit a pronounced stimulus-coupled GABA release. Since the cultures may contain a small population of glutamatergic neurons and the GABAergic neurons have a high content of glutamate it was of interest to examine if glutamate in addition to gamma-aminobutyric acid (GABA) could be released from these cultures. The neurons were preloaded with [(3)H]D-aspartate and subsequently its release was followed during depolarization induced by a high potassium concentration or the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonists, AMPA and kainate. Depolarization of the neurons with 55 mM potassium increased the release of [(3)H]D-aspartate by more than 10-fold. When the non-specific calcium-channel blockers cobalt or lanthanum were included in the stimulation buffer with potassium, the release of [(3)H]D-aspartate was decreased by about 40%. These results indicated that some of the released [(3)H]D-aspartate might originate from a vesicular pool. When AMPA was applied to the neurons, the release of [(3)H]D-aspartate was increased 2-fold and could not be prevented or decreased by addition of cobalt. Since AMPA has a rapid desensitizing effect on AMPA receptors, it was examined whether AMPA under non-desensitizing conditions was able to induce an increased release of [(3)H]D-aspartate as compared to the conditions of applying AMPA alone. The desensitization of AMPA receptors was blocked by 6-chloro-3,4-dihydro-3-(2-norbornen-5-yl)-2H-1,2, 4-benzothiadiazine-7-sulphonamide-1,1-dioxide (cyclothiazide). Under the non-desensitizing conditions, the AMPA-induced release of [(3)H]D-aspartate was highly enhanced showing about a 10-fold increase over basal release. Addition of cobalt or lanthanum did not decrease the amount of [(3)H]D-aspartate released, indicating that the release originated from a cytoplasmic pool. Kainate, which induces an almost non-desensitizing effect on AMPA receptors, showed similar results as observed for AMPA under non-desensitizing conditions. The NMDA receptor antagonist (5R,10 S)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) had only minor effects on the [(3)H]D-aspartate release induced by AMPA and kainate. Thus, the depolarization-induced release of [(3)H]D-aspartate from cultured GABAergic neurons appears to be caused mainly by reversal of the glutamate transporters.

M3 - Journal article

C2 - 10715585

SN - 0736-5748

VL - 18

SP - 309

EP - 315

JO - International Journal of Developmental Neuroscience

JF - International Journal of Developmental Neuroscience

IS - 2-3

ER -