JN AJP: Endocrinology and Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Neurophysiol 84: 495-512, 2000;
0022-3077/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (41)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kager, H.
Right arrow Articles by Somjen, G. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kager, H.
Right arrow Articles by Somjen, G. G.

The Journal of Neurophysiology Vol. 84 No. 1 July 2000, pp. 495-512
Copyright ©2000 by the American Physiological Society

Simulated Seizures and Spreading Depression in a Neuron Model Incorporating Interstitial Space and Ion Concentrations

H. Kager,1 W. J. Wadman,1 and G. G. Somjen2

 1Institute of Neurobiology, University of Amsterdam, 1098 SM Amsterdam, The Netherlands; and  2Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710

Kager, H., W. J. Wadman, and G. G. Somjen. Simulated Seizures and Spreading Depression in a Neuron Model Incorporating Interstitial Space and Ion Concentrations. J. Neurophysiol. 84: 495-512, 2000. Sustained inward currents in neuronal membranes underlie tonic-clonic seizure discharges and spreading depression (SD). It is not known whether these currents flow through abnormally operating physiological ion channels or through pathological pathways that are not normally present. We have now used the NEURON simulating environment of Hines, Moore, and Carnevale to model seizure discharges and SD. The geometry and electrotonic properties of the model neuron conformed to a hippocampal pyramidal cell. Voltage-controlled transient and persistent sodium currents (INa,T and INa,P), potassium currents (IK,DR and IK,A), and N-methyl-D-aspartate (NMDA) receptor-controlled currents (INMDA), were inserted in the appropriate regions of the model cell. The neuron was surrounded by an interstitial space where extracellular potassium and sodium concentration ([K+]o and [Na+]o) could rise or fall. Changes in intra- and extracellular ion concentrations and the resulting shifts in the driving force for ionic currents were continuously computed based on the amount of current flowing through the membrane. A Na-K exchange pump operated to restore ion balances. In addition, extracellular potassium concentration, [K+]o, was also controlled by a "glial" uptake function. Parameters were chosen to resemble experimental data. As long as [K+]o was kept within limits by the activity of the Na-K pump and the "glial" uptake, a depolarizing current pulse applied to the cell soma evoked repetitive firing that ceased when the stimulating current stopped. If, however, [K+]o was allowed to rise, then a brief pulse provoked firing that outlasted the stimulus. At the termination of such a burst, the cell hyperpolarized and then slowly depolarized and another burst erupted without outside intervention. Such "clonic" bursting could continue indefinitely maintained by an interplay of the rise and fall of potassium and sodium concentrations with membrane currents and threshold levels. SD-like depolarization could be produced in two ways, 1) by a dendritic NMDA-controlled current. Glutamate was assumed to be released in response to rising [K+]o. And 2) by the persistent (i.e., slowly inactivating) Na-current, INa,P. When both INMDA and INa,P were present, the two acted synergistically. We conclude that epileptiform neuronal behavior and SD-like depolarization can be generated by the feedback of ion currents that change ion concentrations, which, in turn, influence ion currents and membrane potentials. The normal stability of brain function must depend on the efficient control of ion activities, especially that of [K+]o.




This article has been cited by other articles:


Home page
 J. Neurosci.Home page
Y. David, L. P. Cacheaux, S. Ivens, E. Lapilover, U. Heinemann, D. Kaufer, and A. Friedman
Astrocytic Dysfunction in Epileptogenesis: Consequence of Altered Potassium and Glutamate Homeostasis?
J. Neurosci., August 26, 2009; 29(34): 10588 - 10599.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
F. Frohlich, M. Bazhenov, V. Iragui-Madoz, and T. J. Sejnowski
Potassium Dynamics in the Epileptic Cortex: New Insights on an Old Topic
Neuroscientist, October 1, 2008; 14(5): 422 - 433.
[Abstract] [PDF]

Home page
 J. Neurosci.Home page
A. Qian and J. W. Johnson
Permeant Ion Effects on External Mg2+ Block of NR1/2D NMDA Receptors.
J. Neurosci., October 18, 2006; 26(42): 10899 - 10910.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
P. Sturm, S. Wimmers, J. R Schwarz, and C. K Bauer
Extracellular potassium effects are conserved within the rat erg K+ channel family
J. Physiol., April 15, 2005; 564(2): 329 - 345.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
L. C. Faria and I. Mody
Protective Effect of Ifenprodil Against Spreading Depression in the Mouse Entorhinal Cortex
J Neurophysiol, October 1, 2004; 92(4): 2610 - 2614.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
M. Bazhenov, I. Timofeev, M. Steriade, and T. J. Sejnowski
Potassium Model for Slow (2-3 Hz) In Vivo Neocortical Paroxysmal Oscillations
J Neurophysiol, August 1, 2004; 92(2): 1116 - 1132.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
J. E. Fox, M. Bikson, and J. G. R. Jefferys
Tissue Resistance Changes and the Profile of Synchronized Neuronal Activity During Ictal Events in the Low-Calcium Model of Epilepsy
J Neurophysiol, July 1, 2004; 92(1): 181 - 188.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
M. Bikson, P. J. Hahn, J. E. Fox, and J. G.R. Jefferys
Depolarization Block of Neurons During Maintenance of Electrographic Seizures
J Neurophysiol, October 1, 2003; 90(4): 2402 - 2408.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
H. Kager, W. J. Wadman, and G. G. Somjen
Conditions for the Triggering of Spreading Depression Studied With Computer Simulations
J Neurophysiol, November 1, 2002; 88(5): 2700 - 2712.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
G. G. Somjen
Ion Regulation in the Brain: Implications for Pathophysiology
Neuroscientist, June 1, 2002; 8(3): 254 - 267.
[Abstract] [PDF]

Home page
 J. Physiol.Home page
A. Qian, S. M Antonov, and J. W Johnson
Modulation by permeant ions of Mg2+ inhibition of NMDA-activated whole-cell currents in rat cortical neurons
J. Physiol., January 1, 2002; 538(1): 65 - 77.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
G. G. Somjen
Mechanisms of Spreading Depression and Hypoxic Spreading Depression-Like Depolarization
Physiol Rev, July 1, 2001; 81(3): 1065 - 1096.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
M. Muller and G. G. Somjen
Na+ Dependence and the Role of Glutamate Receptors and Na+ Channels in Ion Fluxes During Hypoxia of Rat Hippocampal Slices
J Neurophysiol, October 1, 2000; 84(4): 1869 - 1880.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online