Abstract
Intracellular Na+ concentration plays an important role in the regulation of cellular energy metabolism; i.e., increased intracellular Na+ concentration stimulates glucose utilization both in cultured neurons and astrocytes. Both high KCl and veratridine, which have been known to cause neuronal damage, elicit increased glucose utilization, presumably via increased intracellular Na+ concentration. In the present study, we examined the role of intracellular Na+ influx in the mechanisms of neuronal cell damage induced by high KCl or veratridine assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric method. Rat primary cultures of striatal neurons were incubated with high KCl (final concentrations: 25, 50 mM) or veratridine (0.1-100 μM) with or without various inhibitors. High KCl depolarizes cell membrane, thus, leading to Na+ influx through an activation of voltage-sensitive Na+ channels, while veratridine elicits Na+ influx by directly opening these channels. After 24-h incubation with elevated [K+](o) or veratridine, glucose contents in the medium decreased significantly (approximately by 7 mM), but remained higher than 18 mM. High [K+](o) reduced percent cell viability significantly (~50% at 25 mM, ~40% at 50 mM [K+](o), P<0.01), but tetrodotoxin (100 nM) had no protective effect, indicating that Na+ influx was not essential to high K+-induced cell death. dl-2-Amino-5-phosponovaleric acid (APV) (1 mM) completely blocked cell death induced by elevated [K+](o), while 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 μM) did not. In contrast, veratridine (>10 μM) caused cell damage in a dose-dependent and tetrodotoxin-sensitive manner, but none of APV, CNQX, or bepridil (Na+-Ca2+ exchanger blocker) had any protective effect. Nifedipine (50~100 μM), however, reduced percent cell damage induced by veratridine. Copyright (C) 1999 Elsevier Science B.V.
| Original language | English |
|---|---|
| Pages (from-to) | 297-304 |
| Number of pages | 8 |
| Journal | European Journal of Pharmacology |
| Volume | 372 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 1999 |
| Externally published | Yes |
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Keywords
- Ca
- K, extracellular
- MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)
- Na channel, voltage-sensitive
- Tetrodotoxin
- Veratridine
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
Role of sodium ion influx in depolarization-induced neuronal cell death by high KCl or veratridine. / Takahashi, S.; Shibata, Mamoru; Fukuuchi, Y.
In: European Journal of Pharmacology, Vol. 372, No. 3, 1999, p. 297-304.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of sodium ion influx in depolarization-induced neuronal cell death by high KCl or veratridine
AU - Takahashi, S.
AU - Shibata, Mamoru
AU - Fukuuchi, Y.
PY - 1999
Y1 - 1999
N2 - Intracellular Na+ concentration plays an important role in the regulation of cellular energy metabolism; i.e., increased intracellular Na+ concentration stimulates glucose utilization both in cultured neurons and astrocytes. Both high KCl and veratridine, which have been known to cause neuronal damage, elicit increased glucose utilization, presumably via increased intracellular Na+ concentration. In the present study, we examined the role of intracellular Na+ influx in the mechanisms of neuronal cell damage induced by high KCl or veratridine assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric method. Rat primary cultures of striatal neurons were incubated with high KCl (final concentrations: 25, 50 mM) or veratridine (0.1-100 μM) with or without various inhibitors. High KCl depolarizes cell membrane, thus, leading to Na+ influx through an activation of voltage-sensitive Na+ channels, while veratridine elicits Na+ influx by directly opening these channels. After 24-h incubation with elevated [K+](o) or veratridine, glucose contents in the medium decreased significantly (approximately by 7 mM), but remained higher than 18 mM. High [K+](o) reduced percent cell viability significantly (~50% at 25 mM, ~40% at 50 mM [K+](o), P<0.01), but tetrodotoxin (100 nM) had no protective effect, indicating that Na+ influx was not essential to high K+-induced cell death. dl-2-Amino-5-phosponovaleric acid (APV) (1 mM) completely blocked cell death induced by elevated [K+](o), while 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 μM) did not. In contrast, veratridine (>10 μM) caused cell damage in a dose-dependent and tetrodotoxin-sensitive manner, but none of APV, CNQX, or bepridil (Na+-Ca2+ exchanger blocker) had any protective effect. Nifedipine (50~100 μM), however, reduced percent cell damage induced by veratridine. Copyright (C) 1999 Elsevier Science B.V.
AB - Intracellular Na+ concentration plays an important role in the regulation of cellular energy metabolism; i.e., increased intracellular Na+ concentration stimulates glucose utilization both in cultured neurons and astrocytes. Both high KCl and veratridine, which have been known to cause neuronal damage, elicit increased glucose utilization, presumably via increased intracellular Na+ concentration. In the present study, we examined the role of intracellular Na+ influx in the mechanisms of neuronal cell damage induced by high KCl or veratridine assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric method. Rat primary cultures of striatal neurons were incubated with high KCl (final concentrations: 25, 50 mM) or veratridine (0.1-100 μM) with or without various inhibitors. High KCl depolarizes cell membrane, thus, leading to Na+ influx through an activation of voltage-sensitive Na+ channels, while veratridine elicits Na+ influx by directly opening these channels. After 24-h incubation with elevated [K+](o) or veratridine, glucose contents in the medium decreased significantly (approximately by 7 mM), but remained higher than 18 mM. High [K+](o) reduced percent cell viability significantly (~50% at 25 mM, ~40% at 50 mM [K+](o), P<0.01), but tetrodotoxin (100 nM) had no protective effect, indicating that Na+ influx was not essential to high K+-induced cell death. dl-2-Amino-5-phosponovaleric acid (APV) (1 mM) completely blocked cell death induced by elevated [K+](o), while 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 μM) did not. In contrast, veratridine (>10 μM) caused cell damage in a dose-dependent and tetrodotoxin-sensitive manner, but none of APV, CNQX, or bepridil (Na+-Ca2+ exchanger blocker) had any protective effect. Nifedipine (50~100 μM), however, reduced percent cell damage induced by veratridine. Copyright (C) 1999 Elsevier Science B.V.
KW - Ca
KW - K, extracellular
KW - MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)
KW - Na channel, voltage-sensitive
KW - Tetrodotoxin
KW - Veratridine
UR - http://www.scopus.com/inward/record.url?scp=0033035647&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033035647&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(99)00208-3
DO - 10.1016/S0014-2999(99)00208-3
M3 - Article
C2 - 10395025
AN - SCOPUS:0033035647
VL - 372
SP - 297
EP - 304
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -