Axon initial segment dysfunction in a mouse model of genetic epilepsy with febrile seizures plus.

The Journal of Clinical Investigation
Verena C WimmerSteven Petrou

Abstract

Febrile seizures are a common childhood seizure disorder and a defining feature of genetic epilepsy with febrile seizures plus (GEFS+), a syndrome frequently associated with Na+ channel mutations. Here, we describe the creation of a knockin mouse heterozygous for the C121W mutation of the beta1 Na+ channel accessory subunit seen in patients with GEFS+. Heterozygous mice with increased core temperature displayed behavioral arrest and were more susceptible to thermal challenge than wild-type mice. Wild-type beta1 was most concentrated in the membrane of axon initial segments (AIS) of pyramidal neurons, while the beta1(C121W) mutant subunit was excluded from AIS membranes. In addition, AIS function, an indicator of neuronal excitability, was substantially enhanced in hippocampal pyramidal neurons of the heterozygous mouse specifically at higher temperatures. Computational modeling predicted that this enhanced excitability was caused by hyperpolarized voltage activation of AIS Na+ channels. This heat-sensitive increased neuronal excitability presumably contributed to the heightened thermal seizure susceptibility and epileptiform discharges seen in patients and mice with beta1(C121W) subunits. We therefore conclude that Na+ channel ...Continue Reading

References

May 1, 1991·Epilepsia·T MorimotoH Matsuda
Sep 3, 1999·The Journal of Biological Chemistry·Z C XiaoL L Isom
Nov 5, 2003·Biology of the Cell·Juan José GarridoBénédicte Dargent
Feb 6, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jérôme J DevauxSteven S Scherer
Apr 23, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chunling ChenLori L Isom
Sep 29, 2004·Pflügers Archiv : European journal of physiology·Verena C WimmerThomas Kuner
Oct 7, 2004·Biophysical Journal·W Zhou, A L Goldin
Oct 7, 2004·The Journal of Biological Chemistry·Dyke P McEwen, Lori L Isom
Nov 5, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·J SpampanatoM H Meisler
Feb 1, 2006·Brain : a Journal of Neurology·Céline DubéTallie Z Baram
Feb 10, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lucy M Palmer, Greg J Stuart
Mar 10, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Arthur J BarelaAndrew Escayg
Oct 6, 2006·Brain : a Journal of Neurology·Ingrid E SchefferSamuel F Berkovic
Nov 18, 2006·The Journal of Comparative Neurology·Audra Van WartGary Matthews
Dec 8, 2006·Nature·Ed S LeinAllan R Jones
Feb 23, 2007·Journal of Neurophysiology·Julian P Meeks, Steven Mennerick
Jun 1, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ikuo OgiwaraKazuhiro Yamakawa
Jan 22, 2008·Nature Neuroscience·Maarten H P KoleGreg J Stuart
May 10, 2008·The Journal of Clinical Investigation·Hiroshi WatanabeConnie R Bezzina
Jul 16, 2008·Molecular and Cellular Neurosciences·Amandine DuflocqMarc Davenne
Jul 25, 2008·Journal of Neurophysiology·Michel RoyeckHeinz Beck
Aug 13, 2008·Expert Opinion on Therapeutic Targets·William J Brackenbury, Lori L Isom
Sep 20, 2008·Current Opinion in Neurobiology·Yasuhiro Ogawa, Matthew N Rasband
Oct 23, 2008·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·William J BrackenburyLori L Isom
Jan 2, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andrea Lorincz, Zoltan Nusser
Feb 3, 2009·Neuron·Kevin J Bender, Laurence O Trussell
Feb 11, 2009·Brain & Development·Ingrid E SchefferLeanne Dibbens
Feb 21, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Teresa K AmanIndira M Raman
Feb 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·John C OakleyWilliam A Catterall
Aug 28, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gustavo A PatinoLori L Isom

❮ Previous
Next ❯

Citations

Apr 16, 2013·Journal of Bioenergetics and Biomembranes·Debora BaroniOscar Moran
Jan 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·William J BrackenburyLori L Isom
Sep 11, 2012·Brain : a Journal of Neurology·Niels EijkelkampJohn N Wood
Oct 14, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gustavo A PatinoLori L Isom
Oct 12, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lei SunRobert Reenan
Nov 11, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Matthew S GrubbKevin J Bender
Mar 4, 2014·Comptes rendus biologies·Qian LiuJing-Hai Zhang
Dec 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·John GilchristFrank Bosmans
Apr 22, 2014·Brain : a Journal of Neurology·Christopher A ReidSteven Petrou
Dec 10, 2015·Scientific Reports·Michael S HildebrandChristopher A Reid
May 28, 2011·British Journal of Pharmacology·Christopher A ReidSteven Petrou
Apr 23, 2013·Epilepsy Research·Rosemary C HartyVerena C Wimmer
Jun 5, 2015·Frontiers in Pharmacology·Debora Baroni, Oscar Moran
May 31, 2012·Channels·Csilla Egri, Peter C Ruben
Jan 31, 2012·Neuron·Maarten H P Kole, Greg J Stuart
Feb 11, 2015·Annual Review of Physiology·Heather A O'Malley, Lori L Isom
Oct 25, 2016·British Journal of Pharmacology·Christopher A ReidSteven Petrou
Jun 3, 2017·Neuropharmacology·Benedetta TerragniMassimo Mantegazza
Aug 23, 2017·Neuroscience Bulletin·Yu GuoYan Zhang
Sep 25, 2018·Journal of Neurogenetics·Jeffrey D Calhoun, Gemma L Carvill
Dec 22, 2017·Pharmacological Reviews·Julia OyrerChristopher A Reid
Nov 12, 2019·Annals of Clinical and Translational Neurology·Alec AebyLori L Isom
Oct 17, 2019·Biomolecules·Eric CortadaMarcel Verges
Nov 23, 2011·The European Journal of Neuroscience·Shelly A Buffington, Matthew N Rasband
May 5, 2016·Cold Spring Harbor Perspectives in Medicine·David I KaplanSteven Petrou
Mar 24, 2017·Epilepsy Currents·Jennifer A Kearney
Dec 11, 2020·Neurobiology of Disease·Wanqi Wang, Wayne N Frankel
May 27, 2021·Human Heredity·Hisham Al-WardHui Xu

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

Prism
ImageJ
GraphPad
pClamp
Windows
MATLAB
NEURON
Huygens Essential

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The Journal of Physiology
Verena C WimmerSteven Petrou
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Gustavo A PatinoLori L Isom
Proceedings of the National Academy of Sciences of the United States of America
William J BrackenburyLori L Isom
© 2021 Meta ULC. All rights reserved