 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 11, 2545-2551, Copyright © 1991 by Society for Neuroscience
Intracellular calcium concentrations during "chemical hypoxia" and excitotoxic neuronal injury
JM Dubinsky and SM Rothman
Departments of Anatomy, Washington University School of Medicine, St Louis, Missouri 63110.
Because hypoxic/ischemic neurodegeneration appears to be in part linked to
glutamate neurotoxicity, we measured intracellular calcium (Ca2+i) levels
in cultured hippocampal neurons during exposure to toxic doses of glutamate
(GLU) and to an anoxic environment simulated by sodium cyanide (NaCN).
Changes in Ca2+i produced by cyanide greatly exceeded those induced by GLU.
The NaCN response was mimicked when oxidative metabolism was also disrupted
by sodium azide, oligomycin, or dinitrophenol. Noncompetitive NMDA receptor
antagonists and enzymatic GLU degradation abolished the GLU-induced Ca2+i
increases and attenuated those produced by NaCN. Only NaCN-induced
increases were blocked when dantrolene and ruthenium red were applied to
prevent release from intracellular pools. All responses were reduced
proportionally in the absence of added external calcium. These results
suggest that extracellular GLU accumulation and subsequent activation of
GLU receptors were involved in the NaCN response. During such metabolic
compromise, however, GLU-induced elevations of Ca2+i were enormously
amplified. In parallel toxicity studies, NaCN was not neurotoxic despite
the large elevations in Ca2+i, indicating that a general elevation in
cytoplasmic calcium does not necessarily predict neurodegeneration.
This article has been cited by other articles:
|
|
|
|
 
M. Henrich and K. J. Buckler
Effects of Anoxia and Aglycemia on Cytosolic Calcium Regulation in Rat Sensory Neurons
J Neurophysiol,
July 1, 2008;
100(1):
456 - 473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Verkhratsky
Physiology and Pathophysiology of the Calcium Store in the Endoplasmic Reticulum of Neurons
Physiol Rev,
January 1, 2005;
85(1):
201 - 279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Matsumoto, S. Yamamoto, Y. Suzuki, T. Tsuboi, S. Terakawa, N. Ohashi, and K. Umemura
Na+/H+ Exchanger Inhibitor, SM-20220, Is Protective Against Excitotoxicity in Cultured Cortical Neurons
Stroke,
January 1, 2004;
35(1):
185 - 190.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Nicotera
Molecular Switches Deciding the Death of Injured Neurons
Toxicol. Sci.,
July 1, 2003;
74(1):
4 - 9.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. P. Mark, R. W. Prost, J. L. Ulmer, M. M. Smith, D. L. Daniels, J. M. Strottmann, W. D. Brown, and L. Hacein-Bey
Pictorial Review of Glutamate Excitotoxicity: Fundamental Concepts for Neuroimaging
AJNR Am. J. Neuroradiol.,
November 1, 2001;
22(10):
1813 - 1824.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Aizenman, J. D. Sinor, J. C. Brimecombe, and G. A. Herin
Alterations of N-Methyl-D-aspartate Receptor Properties after Chemical Ischemia
J. Pharmacol. Exp. Ther.,
November 1, 2000;
295(2):
572 - 577.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. W. Ward, A. C. Rego, B. G. Frenguelli, and D. G. Nicholls
Mitochondrial Membrane Potential and Glutamate Excitotoxicity in Cultured Cerebellar Granule Cells
J. Neurosci.,
October 1, 2000;
20(19):
7208 - 7219.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Jabaudon, M. Scanziani, B. H. Gahwiler, and U. Gerber
Acute decrease in net glutamate uptake during energy deprivation
PNAS,
May 9, 2000;
97(10):
5610 - 5615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Connor and R. J. Cormier
Cumulative Effects of Glutamate Microstimulation on Ca2+ Responses of CA1 Hippocampal Pyramidal Neurons in Slice
J Neurophysiol,
January 1, 2000;
83(1):
90 - 98.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. G. Nicholls and S. L. Budd
Mitochondria and Neuronal Survival
Physiol Rev,
January 1, 2000;
80(1):
315 - 360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tanabe, M. Mori, B. H. Gahwiler, and U. Gerber
Apamin-Sensitive Conductance Mediates the K+ Current Response During Chemical Ischemia in CA3 Pyramidal Cells
J Neurophysiol,
December 1, 1999;
82(6):
2876 - 2882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Blalock, N. M. Porter, and P. W. Landfield
Decreased G-Protein-Mediated Regulation and Shift in Calcium Channel Types with Age in Hippocampal Cultures
J. Neurosci.,
October 1, 1999;
19(19):
8674 - 8684.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhang and P. Lipton
Cytosolic Ca2+ Changes during In Vitro Ischemia in Rat Hippocampal Slices: Major Roles for Glutamate and Na+-Dependent Ca2+ Release from Mitochondria
J. Neurosci.,
May 1, 1999;
19(9):
3307 - 3315.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tekkok, I. Medina, and K. Krnjevic
Intraneuronal [Ca2+] Changes Induced by 2-Deoxy-D-Glucose in Rat Hippocampal Slices
J Neurophysiol,
January 1, 1999;
81(1):
174 - 183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Carriedo, H. Z. Yin, S. L. Sensi, and J. H. Weiss
Rapid Ca2+ Entry through Ca2+-Permeable AMPA/Kainate Channels Triggers Marked Intracellular Ca2+ Rises and Consequent Oxygen Radical Production
J. Neurosci.,
October 1, 1998;
18(19):
7727 - 7738.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fern
Intracellular Calcium and Cell Death during Ischemia in Neonatal Rat White Matter Astrocytes In Situ
J. Neurosci.,
September 15, 1998;
18(18):
7232 - 7243.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Arden, J. D. Sinor, W. K. Potthoff, and E. Aizenman
Subunit-specific Interactions of Cyanide with the N-Methyl-D-aspartate Receptor
J. Biol. Chem.,
August 21, 1998;
273(34):
21505 - 21511.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Erdemli and V. Crunelli
Response of Thalamocortical Neurons to Hypoxia: A Whole-Cell Patch-Clamp Study
J. Neurosci.,
July 15, 1998;
18(14):
5212 - 5224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Pisani, P. Calabresi, A. Tozzi, V. D'Angelo, G. Bernardi, and C. Iadecola
L-Type Ca2+ Channel Blockers Attenuate Electrical Changes and Ca2+ Rise Induced by Oxygen/Glucose Deprivation in Cortical Neurons • Editorial Comment
Stroke,
January 1, 1998;
29(1):
196 - 202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Pombo, T. Tsujita, J. M. Kyriakis, J. V. Bonventre, and T. Force
Activation of the Ste20-like Oxidant Stress Response Kinase-1 during the Initial Stages of Chemical Anoxia-induced Necrotic Cell Death. REQUIREMENT FOR DUAL INPUTS OF OXIDANT STRESS AND INCREASED CYTOSOLIC [Ca2+]
J. Biol. Chem.,
November 14, 1997;
272(46):
29372 - 29379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Murai, H. Ishibashi, S. Koyama, and N. Akaike
Ca2+-Activated K+ Currents in Rat Locus Coeruleus Neurons Induced by Experimental Ischemia, Anoxia, and Hypoglycemia
J Neurophysiol,
November 1, 1997;
78(5):
2674 - 2681.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Hyrc, S. D. Handran, S. M. Rothman, and M. P. Goldberg
Ionized Intracellular Calcium Concentration Predicts Excitotoxic Neuronal Death: Observations with Low-Affinity Fluorescent Calcium Indicators
J. Neurosci.,
September 1, 1997;
17(17):
6669 - 6677.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yamamoto, E. Tanaka, Y. Shoji, Y. Kudo, H. Inokuchi, and H. Higashi
Factors That Reverse the Persistent Depolarization Produced by Deprivation of Oxygen and Glucose in Rat Hippocampal CA1 Neurons In Vitro
J Neurophysiol,
August 1, 1997;
78(2):
903 - 911.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Zhu
Adenosine Release Mediates Cyanide-Induced Suppression of CA1 Neuronal Activity
J. Neurosci.,
April 1, 1997;
17(7):
2355 - 2364.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Sun, S. G. Rane, P. G. Gunasekar, J. L. Borowitz, and G. E. Isom
Modulation of the NMDA Receptor by Cyanide: Enhancement of Receptor-Mediated Responses
J. Pharmacol. Exp. Ther.,
March 1, 1997;
280(3):
1341 - 1348.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Yamamoto, E. Tanaka, and H. Higashi
Mediation by Intracellular Calcium-Dependent Signals of Hypoxic Hyperpolarization in Rat Hippocampal CA1 Neurons In Vitro
J Neurophysiol,
January 1, 1997;
77(1):
386 - 392.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Xiang, D. W. Hochman, H. Saya, T. Fujiwara, P. A. Schwartzkroin, and R. S. Morrison
Evidence for p53-Mediated Modulation of Neuronal Viability
J. Neurosci.,
November 1, 1996;
16(21):
6753 - 6765.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. F. Schinder, E. C. Olson, N. C. Spitzer, and M. Montal
Mitochondrial Dysfunction Is a Primary Event in Glutamate Neurotoxicity
J. Neurosci.,
October 1, 1996;
16(19):
6125 - 6133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. M. Lu, H. Z. Yin, J. Chiang, and J. H. Weiss
Ca2+-Permeable AMPA/Kainate and NMDA Channels: High Rate of Ca2+ Influx Underlies Potent Induction of Injury
J. Neurosci.,
September 1, 1996;
16(17):
5457 - 5465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Lipton and P. A. Rosenberg
Excitatory Amino Acids as a Final Common Pathway for Neurologic Disorders
N. Engl. J. Med.,
March 3, 1994;
330(9):
613 - 622.
[Full Text]
|
|
|
|
