Extracellular pH modulates N-methyl-d-aspartate receptor-mediated neurotoxicity and calcium accumulation in rat cortical cultures

Takadera, Tsuneo; Shimada, Yumiko; Mohri, Tetsuro

doi:10.1016/0006-8993(92)90460-q

Cited by 37 publications

(17 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We were able to confirm previous findings that increasing pH between 6.5 and 8.0 enhances NMDA-induced [Ca2+]J changes (Takadera et al, 1992). Moreover, we did not find any evidence to suggest that changing extracellular pH had any effect on the ability of neurones to clear Ca2" from the cytoplasm, as indicated by the identical rates of recovery of responses following washout of agonists (Table 2).…”

Section: Discussionsupporting

confidence: 87%

Effects of pH on the actions of dizocilpine at the N‐methyl‐D‐aspartate receptor complex

Rajdev

Reynolds

1993

British J Pharmacology

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 87%

Effects of pH on the actions of dizocilpine at the N‐methyl‐D‐aspartate receptor complex

Rajdev

Reynolds

1993

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…1). These data indicate that the cerebral cortical neurons used in this study are susceptible to the neurotoxicity in duced by NMDA as previously reported (14,15). In the cases of the control and the group treated with MK-801 alone, LDH leakage was also observed (Figs.…”

supporting

confidence: 89%

Muscimol Prevents Neuronal Injury Induced by NMDA

Ohkuma

Chen

Katsura

et al. 1994

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-The effect of muscimol on N-methyl-D-aspartate (NMDA)-induced injury of primary cultured cerebral cortical neurons was examined. NMDA induced a dose-dependent leakage of LDH activ ity, which was significantly inhibited by (±)-5-methyl-10,11-dihydro-5H-dibenzo- [a,d]cyclopentan-5,10-imine (MK-801). Muscimol significantly reduced the NMDA-induced increase of lactic dehydrogenase (LDH) leakage, and bicuculline abolished this protective effect of muscimol. Similarly, muscimol reduced the NMDA-induced increase in trypan blue staining of the cells, and bicuculline suppressed this inhibitory ac tion of muscimol. These results suggest that GABAA-receptor stimulation exerts a protective action against the neuronal injury induced by NMDA-receptor activation.Keywords: GABAA-receptor agonist, NMDA receptor, Neuronal injuryThe N-methyl-D-aspartate (NMDA) receptor, a sub type of glutamate receptors, has been supposed to par ticipate in the neuronal cell damage observed in central nervous system disorders such as Huntington's disease, epilepsy, parkinsonism, ischemia and trauma (1 -4). The excessive accumulation of Ca" in neuronal cells induced by over-activation of NMDA receptors under the patho logical conditions results in the neuronal injury (1, 2). On the other hand, an inhibitory receptor, GABAA receptor, has been reported to negatively regulate excitatory func tions of NMDA receptors (5 7). This suggests that GABAA-receptor stimulation may suppress the excitatory actions of NMDA receptors, especially NMDA-induced neuronal toxicity. In the present study, we examined the effect of GABAA-receptor activation on NMDA-induced neuronal injury by measuring the leakage of lactic de hydrogenase (LDH) activity from primary cultured mouse cerebral cortical neurons and the staining of the neurons with trypan blue dye.Cell isolation and primary culture were carried out by the previously reported procedures (8). In brief, the neo pallium free of meninges dissected from 15-day-old fetuses of ddY strain mice were minced, trypsinized and centrifuged. Collected cells were incubated in Dulbecco's modified Eagle medium (DMEM) supplemented with 15% fetal calf serum at 371C for 3 days in humidified 95% air 5 °1o C02, followed by the exposure to 10 uM cytosine arabinoside for 24 hr to suppress the proliferation of non neuronal cells. Neurons were then cultured in DMEM con taining 10% horse serum under the culture conditions described above until they were used for the experiments. The culture medium was exchanged every 4 days. All neu rons used in the experiments were from 13-day-old cell cul tures.For measuring the leakage of LDH activity from neu rons, the neurons were exposed to NMDA by the previous ly reported method (9) with a minor modification. Neu rons were washed 3 times with ice-cold, Mg2+-free Krebs Ringer bicarbonate buffer (KRB: pH 7.4) and then pre incubated with Mg2+-free KRB at 37 C for 10 min. There after, the neurons were incubated with NMDA and other agents for 15 min. Following this incubation, the incuba tion medi...

show abstract

“…- 23 It is therefore not surprising that our results differ from those of Takadera et al 10 or Giffard et al, 9 who examined only the effects of pH on NMDA-mediated processes.…”

contrasting

confidence: 55%

“…8 Second, low pH in bathing medium reduces calcium influx and cellular injury in cultured neurons during hypoxia, 9 ' 10 possibly by decreasing the activity of the Af-methyl-D-aspartate (NMDA) subtype of glutamate receptor. 912 In these studies, tissues without the complex synaptic function of intact brain were used (ie, cultured neurons or isolated cells), and in only one 10 was pHj measured. The purpose of this study was to examine the influences of both pHj and pHe on changes in cytosolic …”

Section: Influence Of Ph On Calcium Influx During Hypoxia In Rat Cortmentioning

confidence: 99%

Influence of pH on calcium influx during hypoxia in rat cortical brain slices.

O'Donnell

Bickler

1994

Stroke

View full text Add to dashboard Cite

Background and Purpose Acidity of brain intracellular and extracellular fluids appears to increase brain injury from stroke, but low extracellular pH decreases the activity of AT-methyl-D-aspartate receptor ion channels and decreases calcium influx into isolated neurons. To further investigate the role of acid-base balance in hypoxic brain injury, we studied the influences of intracellular and extracellular pH on calcium influx in cortical brain slices during hypoxia.Methods Intracellular calcium ([Ca 2+ ]i) and pH (pH,) were measured fluorometrically with the dyes fura-2 and biscarboxyethyl carboxyfluorescein, respectively, during two types of hypoxia: (1) slice perfusate equilibrated with N 2 /CO 2 at pH 6.6 or 6.2 ("gaseous hypoxia") or (2) perfusate equilibrated with 95% O 2 /5% CO 2 plus 100 jwnol/L NaCN at pH 7.3, 6.6, or 6.2 ("chemical hypoxia").

show abstract

Extracellular pH modulates N-methyl-d-aspartate receptor-mediated neurotoxicity and calcium accumulation in rat cortical cultures

Cited by 37 publications

References 22 publications

Effects of pH on the actions of dizocilpine at the N‐methyl‐D‐aspartate receptor complex

Effects of pH on the actions of dizocilpine at the N‐methyl‐D‐aspartate receptor complex

Muscimol Prevents Neuronal Injury Induced by NMDA

Influence of pH on calcium influx during hypoxia in rat cortical brain slices.

Contact Info

Product

Resources

About