 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
Volume 16, Number 23, Issue of December 1, 1996 pp. 7447-7457
Copyright ©1996 Society for NeuroscienceNMDA Receptor Activation Inhibits Neuronal Volume Regulation after Swelling Induced by Veratridine-Stimulated Na+ Influx in Rat Cortical Cultures
Received June 27, 1996; revised Sept. 6, 1996; accepted Sept. 11, 1996.
Kevin B. Churchwell2, Stephen H. Wright4, Francesco Emma1, Paul A. Rosenberg3, and Kevin Strange1, 2 Departments of 1 Medicine (Nephrology), and 2 Anesthesia,
Critical Care Research Laboratories, 3 Department of Neurology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, and 4 Department of Physiology, University of Arizona, Tucson, Arizona 85724 Neurons and glia experience rapid fluctuations in transmembrane solute and water fluxes during normal brain activity. Cell volume must be regulated under these conditions to maintain optimal neural function. Almost nothing is known, however, about how brain cells respond to volume challenges induced by changes in transmembrane solute flux. As such, we characterized the volume-regulatory mechanisms of cultured cortical neurons swollen by veratridine-stimulated Na+ influx. Exposure of cortical neurons to 100 µM veratridine for 10-15 min caused a 1.8- to 2-fold increase in cell volume that persisted for at least 90 min. This volume increase was blocked by extracellular Na+ removal or by exposure to 5 µM tetrodotoxin, indicating that swelling is a result of Na+ entry via Na+ channels. Treatment of cells with veratridine together with various NMDA receptor antagonists had no effect on the magnitude of swelling. NMDA receptor antagonist-treated cells, however, underwent nearly complete volume recovery within 50-70 min after veratridine exposure. This recovery suggests that NMDA receptor activation disrupts neuronal osmoregulatory pathways. Volume regulation was blocked by Ba2+, quinidine, or 5-nitro-2-(3-phenylpropylamino) benzoic acid, indicating that swelling activates volume regulatory K+ and Cl
channels. Veratridine also caused a rapid, transient increase in intracellular Ca2+. Extracellular Ca2+ removal or intracellular Ca2+ chelation prevented or dramatically reduced veratridine-induced increases in intracellular Ca2+ and completely blocked volume recovery. These findings indicate that increases in Ca2+ during cell swelling induced by Na+ influx are required for activation of neuronal volume-regulatory pathways.
Key words: osmoregulation; edema; excitotoxicity; MK-801
This article has been cited by other articles:
H. Inoue and Y. Okada
Roles of Volume-Sensitive Chloride Channel in Excitotoxic Neuronal Injury
J. Neurosci., February 7, 2007; 27(6): 1445 - 1455.
[Abstract] [Full Text] [PDF]
L. S. Loo and J. O. McNamara
Impaired Volume Regulation is the Mechanism of Excitotoxic Sensitization to Complement
J. Neurosci., October 4, 2006; 26(40): 10177 - 10187.
[Abstract] [Full Text] [PDF]
S. L. Schomberg, J. Bauer, D. B. Kintner, G. Su, A. Flemmer, B. Forbush, and D. Sun
Cross Talk Between the GABAA Receptor and the Na-K-Cl Cotransporter Is Mediated by Intracellular Cl-
J Neurophysiol, January 1, 2003; 89(1): 159 - 167.
[Abstract] [Full Text] [PDF]
A. Y. Xiao, L. Wei, S. Xia, S. Rothman, and S. P. Yu
Ionic Mechanism of Ouabain-Induced Concurrent Apoptosis and Necrosis in Individual Cultured Cortical Neurons
J. Neurosci., February 15, 2002; 22(4): 1350 - 1362.
[Abstract] [Full Text] [PDF]
Y. Okada, E. Maeno, T. Shimizu, K. Dezaki, J. Wang, and S. Morishima
Receptor-mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD)
J. Physiol., April 1, 2001; 532(1): 3 - 16.
[Abstract] [Full Text] [PDF]
A. C. Rego, M. W. Ward, and D. G. Nicholls
Mitochondria Control AMPA/Kainate Receptor-Induced Cytoplasmic Calcium Deregulation in Rat Cerebellar Granule Cells
J. Neurosci., March 15, 2001; 21(6): 1893 - 1901.
[Abstract] [Full Text] [PDF]
X. Wang, A. Y. Xiao, T. Ichinose, and S. P. Yu
Effects of Tetraethylammonium Analogs on Apoptosis and Membrane Currents in Cultured Cortical Neurons
J. Pharmacol. Exp. Ther., November 1, 2000; 295(2): 524 - 530.
[Abstract] [Full Text]
R. Tremblay, B. Chakravarthy, K. Hewitt, J. Tauskela, P. Morley, T. Atkinson, and J. P. Durkin
Transient NMDA Receptor Inactivation Provides Long-Term Protection to Cultured Cortical Neurons from a Variety of Death Signals
J. Neurosci., October 1, 2000; 20(19): 7183 - 7192.
[Abstract] [Full Text] [PDF]
V. V Senatorov, P. K Stys, and B. Hu
Regulation of Na+,K+-ATPase by persistent sodium accumulation in adult rat thalamic neurones
J. Physiol., June 1, 2000; 525(2): 343 - 353.
[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]
P Doroshenko
High intracellular chloride delays the activation of the volume-sensitive chloride conductance in mouse L-fibroblasts
J. Physiol., January 15, 1999; 514(2): 437 - 446.
[Abstract] [Full Text] [PDF]
T. A. Basarsky, S. N. Duffy, R. D. Andrew, and B. A. MacVicar
Imaging Spreading Depression and Associated Intracellular Calcium Waves in Brain Slices
J. Neurosci., September 15, 1998; 18(18): 7189 - 7199.
[Abstract] [Full Text] [PDF]
A. J. Patel, I. Lauritzen, M. Lazdunski, and E. Honore
Disruption of Mitochondrial Respiration Inhibits Volume-Regulated Anion Channels and Provokes Neuronal Cell Swelling
J. Neurosci., May 1, 1998; 18(9): 3117 - 3123.
[Abstract] [Full Text] [PDF]
F. LANG, G. L. BUSCH, M. RITTER, H. VOLKL, S. WALDEGGER, E. GULBINS, and D. HAUSSINGER
Functional Significance of Cell Volume Regulatory Mechanisms
Physiol Rev, January 1, 1998; 78(1): 247 - 306.
[Abstract] [Full Text] [PDF]
C. R. Rose, B. R. Ransom, and S. G. Waxman
Pharmacological Characterization of Na+ Influx via Voltage-Gated Na+ Channels in Spinal Cord Astrocytes
J Neurophysiol, December 1, 1997; 78(6): 3249 - 3258.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|