Am J Physiol Cell Physiol Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 281: C496-C503, 2001;
0363-6143/01 $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 (22)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gu, X. Q.
Right arrow Articles by Haddad, G. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gu, X. Q.
Right arrow Articles by Haddad, G. G.
Vol. 281, Issue 2, C496-C503, August 2001

Increased neuronal excitability and seizures in the Na+/H+ exchanger null mutant mouse

Xiang Q. Gu1, Hang Yao1, and Gabriel G. Haddad1,2

Departments of 1 Pediatrics (Section of Respiratory Medicine) and 2 Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510

Mice lacking the Na+/H+ exchanger isoform 1 (NHE1) manifest neurological diseases that include ataxia, motor deficits, and a seizure disorder. The molecular basis for the phenotype has not been clear, and it has not been determined how the lack of NHE1 leads, in particular, to the seizure disorder. We have shown in this work that hippocampal CA1 neurons in mutant mice have a much higher excitability than in wild-type mice. This higher excitability is partly based on an upregulation of the Na+ current density (608.2 ± 123.2 pA/pF in NHE1 mutant vs. 334.7 ± 63.7 pA/pF in wild type in HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>/CO2). Alterations in Na+ channel characteristics, including steady-state inactivation (shift of 18 mV in the depolarization direction in the mutant), recovery from inactivation (tau h = 5.22 ± 0.49 ms in wild-type neurons and 2.20 ± 0.20 ms in mutant neurons), and deactivation (at -100 mV, tau d = 1.75 ± 0.53 ms in mutant and 0.21 ± 0.05 ms in wild-type neurons) further enhance the differences in excitability between mutant and wild-type mice. Our investigation demonstrates the existence of an important functional interaction between the NHE1 protein and the voltage-sensitive Na+ channel. We hypothesize that the increased neuronal excitability and possibly the seizure disorder in mice lacking the NHE1 is due, at least in part, to changes in Na+ channel expression and/or regulation.

sodium channels; sodium-hydrogen exchanger mutant mice


This article has been cited by other articles:


Home page
 Toxicol PatholHome page
J. C. Pettersen, L. Chouinard, R. L. Kerlin, S. N. Groom, S. Botts, J. C. Arezzo, M. A. Boucher, D. E. Frazier, and A. R. Buchholz
Neurotoxic Effects of Zoniporide: A Selective Inhibitor of the Na+/H+ Exchanger Isoform 1
Toxicol Pathol, June 1, 2008; 36(4): 608 - 619.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
C.-N. Liu and C. J. Somps
Na+/H+ Exchanger-1 Inhibitors Reduce Neuronal Excitability and Alter Na+ Channel Inactivation Properties in Rat Primary Sensory Neurons
Toxicol. Sci., June 1, 2008; 103(2): 346 - 353.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
C. A. Gurnett, R. Veile, J. Zempel, L. Blackburn, M. Lovett, and A. Bowcock
Disruption of Sodium Bicarbonate Transporter SLC4A10 in a Patient With Complex Partial Epilepsy and Mental Retardation
Arch Neurol, April 1, 2008; 65(4): 550 - 553.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. F. Pedersen, M. E. O'Donnell, S. E. Anderson, and P. M. Cala
Physiology and pathophysiology of Na+/H+ exchange and Na+-K+-2Cl- cotransport in the heart, brain, and blood
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R1 - R25.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Hentschke, M. Wiemann, S. Hentschke, I. Kurth, I. Hermans-Borgmeyer, T. Seidenbecher, T. J. Jentsch, A. Gal, and C. A. Hubner
Mice with a Targeted Disruption of the Cl-/HCO3- Exchanger AE3 Display a Reduced Seizure Threshold
Mol. Cell. Biol., January 1, 2006; 26(1): 182 - 191.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
C. L. Brett, M. Donowitz, and R. Rao
Evolutionary origins of eukaryotic sodium/proton exchangers
Am J Physiol Cell Physiol, February 1, 2005; 288(2): C223 - C239.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. Spampanato, J. A. Kearney, G. de Haan, D. P. McEwen, A. Escayg, I. Aradi, B. T. MacDonald, S. I. Levin, I. Soltesz, P. Benna, et al.
A Novel Epilepsy Mutation in the Sodium Channel SCN1A Identifies a Cytoplasmic Domain for {beta} Subunit Interaction
J. Neurosci., November 3, 2004; 24(44): 10022 - 10034.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
D. Zhou, J. Xue, O. Gavrialov, and G. G. Haddad
Na+/H+ exchanger 1 deficiency alters gene expression in mouse brain
Physiol Genomics, August 11, 2004; 18(3): 331 - 339.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
M G de Silva, K Elliott, H-H Dahl, E Fitzpatrick, S Wilcox, M Delatycki, R Williamson, D Efron, M Lynch, and S Forrest
Disruption of a novel member of a sodium/hydrogen exchanger family and DOCK3 is associated with an attention deficit hyperactivity disorder-like phenotype
J. Med. Genet., October 1, 2003; 40(10): 733 - 740.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
Y. Xia, P. Zhao, J. Xue, X. Q. Gu, X. Sun, H. Yao, and G. G. Haddad
Na+ Channel Expression and Neuronal Function in the Na+/H+ Exchanger 1 Null Mutant Mouse
J Neurophysiol, January 1, 2003; 89(1): 229 - 236.
[Abstract] [Full Text] [PDF]


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