A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization
Abstract
The epileptic encephalopathies are a group of highly heterogeneous genetic disorders. The majority of disease-causing mutations alter genes encoding voltage-gated ion channels, neurotransmitter receptors, or synaptic proteins. We have identified a novel de novo pathogenic K+ channel variant in an idiopathic epileptic encephalopathy family. Here, we report the effects of this mutation on channel function and heterologous expression in cell lines. We present a case report of infantile epileptic encephalopathy in a young girl, and trio-exome sequencing to determine the genetic etiology of her disorder. The patient was heterozygous for a de novo missense variant in the coding region of the KCNB1 gene, c.1133T>C. The variant encodes a V378A mutation in the α subunit of the Kv2.1 voltage-gated K+ channel, which is expressed at high levels in central neurons and is an important regulator of neuronal excitability. We found that expression of the V378A variant results in voltage-activated currents that are sensitive to the selective Kv2 channel blocker guangxitoxin-1E. These voltage-activated Kv2.1 V378A currents were nonselective among monovalent cations. Striking cell background–dependent differences in expression and subcellular localization of the V378A mutation were observed in heterologous cells. Further, coexpression of V378A subunits and wild-type Kv2.1 subunits reciprocally affects their respectivemore »
- Authors:
-
- Children’s Mercy Hospital, Kansas City, MO (United States)
- Univ. of California, Davis, CA (United States). Dept. of Neurobiology, Physiology and Behavior. Dept. of Physiology and Membrane Biology. Dept. of Anesthesiology and Pain Medicine
- Children’s Mercy Hospital, Kansas City, MO (United States); University of Missouri, Kansas City, MO (United States)
- Children’s Mercy Hospital, Kansas City, MO (United States); Univ. of Missouri, Kansas City, MO (United States)
- University of California, Davis, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); Clare Giannini Fund; National Institutes of Health (NIH)
- OSTI Identifier:
- 1625214
- Grant/Contract Number:
- AC02-05CH11231; R01 NS042225
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of General Physiology
- Additional Journal Information:
- Journal Volume: 146; Journal Issue: 5; Journal ID: ISSN 0022-1295
- Publisher:
- Rockefeller University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Thiffault, Isabelle, Speca, David J., Austin, Daniel C., Cobb, Melanie M., Eum, Kenneth S., Safina, Nicole P., Grote, Lauren, Farrow, Emily G., Miller, Neil, Soden, Sarah, Kingsmore, Stephen F., Trimmer, James S., Saunders, Carol J., and Sack, Jon T. A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization. United States: N. p., 2015.
Web. doi:10.1085/jgp.201511444.
Thiffault, Isabelle, Speca, David J., Austin, Daniel C., Cobb, Melanie M., Eum, Kenneth S., Safina, Nicole P., Grote, Lauren, Farrow, Emily G., Miller, Neil, Soden, Sarah, Kingsmore, Stephen F., Trimmer, James S., Saunders, Carol J., & Sack, Jon T. A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization. United States. https://doi.org/10.1085/jgp.201511444
Thiffault, Isabelle, Speca, David J., Austin, Daniel C., Cobb, Melanie M., Eum, Kenneth S., Safina, Nicole P., Grote, Lauren, Farrow, Emily G., Miller, Neil, Soden, Sarah, Kingsmore, Stephen F., Trimmer, James S., Saunders, Carol J., and Sack, Jon T. Mon .
"A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization". United States. https://doi.org/10.1085/jgp.201511444. https://www.osti.gov/servlets/purl/1625214.
@article{osti_1625214,
title = {A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization},
author = {Thiffault, Isabelle and Speca, David J. and Austin, Daniel C. and Cobb, Melanie M. and Eum, Kenneth S. and Safina, Nicole P. and Grote, Lauren and Farrow, Emily G. and Miller, Neil and Soden, Sarah and Kingsmore, Stephen F. and Trimmer, James S. and Saunders, Carol J. and Sack, Jon T.},
abstractNote = {The epileptic encephalopathies are a group of highly heterogeneous genetic disorders. The majority of disease-causing mutations alter genes encoding voltage-gated ion channels, neurotransmitter receptors, or synaptic proteins. We have identified a novel de novo pathogenic K+ channel variant in an idiopathic epileptic encephalopathy family. Here, we report the effects of this mutation on channel function and heterologous expression in cell lines. We present a case report of infantile epileptic encephalopathy in a young girl, and trio-exome sequencing to determine the genetic etiology of her disorder. The patient was heterozygous for a de novo missense variant in the coding region of the KCNB1 gene, c.1133T>C. The variant encodes a V378A mutation in the α subunit of the Kv2.1 voltage-gated K+ channel, which is expressed at high levels in central neurons and is an important regulator of neuronal excitability. We found that expression of the V378A variant results in voltage-activated currents that are sensitive to the selective Kv2 channel blocker guangxitoxin-1E. These voltage-activated Kv2.1 V378A currents were nonselective among monovalent cations. Striking cell background–dependent differences in expression and subcellular localization of the V378A mutation were observed in heterologous cells. Further, coexpression of V378A subunits and wild-type Kv2.1 subunits reciprocally affects their respective trafficking characteristics. A recent study reported epileptic encephalopathy-linked missense variants that render Kv2.1 a tonically activated, nonselective cation channel that is not voltage activated. Our findings strengthen the correlation between mutations that result in loss of Kv2.1 ion selectivity and development of epileptic encephalopathy. However, the strong voltage sensitivity of currents from the V378A mutant indicates that the loss of voltage-sensitive gating seen in all other reported disease mutants is not required for an epileptic encephalopathy phenotype. In addition to electrophysiological differences, we suggest that defects in expression and subcellular localization of Kv2.1 V378A channels could contribute to the pathophysiology of this KCNB1 variant.},
doi = {10.1085/jgp.201511444},
journal = {Journal of General Physiology},
number = 5,
volume = 146,
place = {United States},
year = {Mon Oct 26 00:00:00 EDT 2015},
month = {Mon Oct 26 00:00:00 EDT 2015}
}
Works referenced in this record:
Determination of the subunit stoichiometry of a voltage-activated potassium channel
journal, March 1991
- MacKinnon, Roderick
- Nature, Vol. 350, Issue 6315
Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability: Kv2.1 deletion and hyperexcitability
journal, March 2014
- Speca, D. J.; Ogata, G.; Mandikian, D.
- Genes, Brain and Behavior, Vol. 13, Issue 4
Clinical management of epileptic encephalopathies of childhood and infancy
journal, May 2014
- Covanis, Athanasios
- Expert Review of Neurotherapeutics, Vol. 14, Issue 6
A Novel Targeting Signal for Proximal Clustering of the Kv2.1 K+ Channel in Hippocampal Neurons
journal, February 2000
- Lim, Seung T.; Antonucci, Dana E.; Scannevin, Robert H.
- Neuron, Vol. 25, Issue 2
How to Validate a Heteromeric Ion Channel Drug Target: Assessing Proper Expression of Concatenated Subunits
journal, April 2008
- Sack, Jon T.; Shamotienko, Oleg; Dolly, J. Oliver
- Journal of General Physiology, Vol. 131, Issue 5
Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding.
journal, January 1992
- Ridgway, N. D.; Dawson, P. A.; Ho, Y. K.
- Journal of Cell Biology, Vol. 116, Issue 2
Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm
journal, June 2009
- Kumar, Prateek; Henikoff, Steven; Ng, Pauline C.
- Nature Protocols, Vol. 4, Issue 7
Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009
journal, April 2010
- Berg, Anne T.; Berkovic, Samuel F.; Brodie, Martin J.
- Epilepsia, Vol. 51, Issue 4
Targeting F508del-CFTR to develop rational new therapies for cystic fibrosis
journal, June 2011
- Cai, Zhi-wei; Liu, Jia; Li, Hong-yu
- Acta Pharmacologica Sinica, Vol. 32, Issue 6
Interactions between lipids and voltage sensor paddles detected with tarantula toxins
journal, September 2009
- Milescu, Mirela; Bosmans, Frank; Lee, Seungkyu
- Nature Structural & Molecular Biology, Vol. 16, Issue 10
De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies
journal, October 2014
- Appenzeller, Silke; Balling, Rudi; Barisic, Nina
- The American Journal of Human Genetics, Vol. 95, Issue 4
Cell type-specific spatial and functional coupling between mammalian brain Kv2.1 K + channels and ryanodine receptors: Coupling of Neuronal K + Channels and RyRs
journal, July 2014
- Mandikian, Danielle; Bocksteins, Elke; Parajuli, Laxmi Kumar
- Journal of Comparative Neurology, Vol. 522, Issue 15
Regulation of Kvl channel trafficking by the mamba snake neurotoxin dendrotoxin K
journal, December 2006
- Vacher, Helene; Mohapatra, Durga P.; Misonou, Hiroaki
- The FASEB Journal, Vol. 21, Issue 3
Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons
journal, April 2014
- Liu, Pin W.; Bean, Bruce P.
- The Journal of Neuroscience, Vol. 34, Issue 14
A Gastropod Toxin Selectively Slows Early Transitions in the Shaker K Channel's Activation Pathway
journal, May 2004
- Sack, Jon T.; Aldrich, Richard W.; Gilly, William F.
- Journal of General Physiology, Vol. 123, Issue 6
Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing
journal, January 2011
- Bell, C. J.; Dinwiddie, D. L.; Miller, N. A.
- Science Translational Medicine, Vol. 3, Issue 65
Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity
journal, January 2015
- Trimmer, James S.
- Neuron, Vol. 85, Issue 2
Frequency-dependent regulation of rat hippocampal somato-dendritic excitability by the K + channel subunit Kv2.1
journal, January 2000
- Du, Jing; Haak, Laurel L.; Phillips-Tansey, Emily
- The Journal of Physiology, Vol. 522, Issue 1
Blockers of the Delayed-Rectifier Potassium Current in Pancreatic -Cells Enhance Glucose-Dependent Insulin Secretion
journal, March 2006
- Herrington, J.; Zhou, Y. -P.; Bugianesi, R. M.
- Diabetes, Vol. 55, Issue 4
Heteromultimeric channels formed by rat brain potassium-channel proteins
journal, June 1990
- Ruppersberg, J. Peter; Schröter, Klaus H.; Sakmann, Bert
- Nature, Vol. 345, Issue 6275
Tarantula toxins use common surfaces for interacting with Kv and ASIC ion channels
journal, May 2015
- Gupta, Kanchan; Zamanian, Maryam; Bae, Chanhyung
- eLife, Vol. 4
Delayed Rectifier K + Currents, I K , Are Encoded by Kv2 α-Subunits and Regulate Tonic Firing in Mammalian Sympathetic Neurons
journal, December 2002
- Malin, Sacha A.; Nerbonne, Jeanne M.
- The Journal of Neuroscience, Vol. 22, Issue 23
Immunological identification and characterization of a delayed rectifier K+ channel polypeptide in rat brain.
journal, December 1991
- Trimmer, J. S.
- Proceedings of the National Academy of Sciences, Vol. 88, Issue 23
Induction of stable ER-plasma-membrane junctions by Kv2.1 potassium channels
journal, April 2015
- Fox, P. D.; Haberkorn, C. J.; Akin, E. J.
- Journal of Cell Science, Vol. 128, Issue 11
Potassium channel genes and benign familial neonatal epilepsy
book, January 2014
- Maljevic, Snezana; Lerche, Holger
- Progress in Brain Research
Chemoselective tarantula toxins report voltage activation of wild-type ion channels in live cells
journal, October 2014
- Tilley, D. C.; Eum, K. S.; Fletcher-Taylor, S.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 44
De novo KCNB1 mutations in epileptic encephalopathy: KCNB1 Mutations
journal, September 2014
- Torkamani, Ali; Bersell, Kevin; Jorge, Benjamin S.
- Annals of Neurology, Vol. 76, Issue 4
The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ
journal, January 2008
- Sarmiere, Patrick D.; Weigle, Cecile M.; Tamkun, Michael M.
- BMC Neuroscience, Vol. 9, Issue 1
A method and server for predicting damaging missense mutations
journal, April 2010
- Adzhubei, Ivan A.; Schmidt, Steffen; Peshkin, Leonid
- Nature Methods, Vol. 7, Issue 4
A brefeldin A-like phenotype is induced by the overexpression of a human ERD-2-like protein, ELP-1
journal, May 1992
- Hsu, Victor W.; Shah, Nicky; Klausner, Richard D.
- Cell, Vol. 69, Issue 4
Properties of Kv2.1 K+ channels expressed in transfected mammalian cells.
journal, September 1994
- Shi, G.; Kleinklaus, A. K.; Marrion, N. V.
- Journal of Biological Chemistry, Vol. 269, Issue 37
Axon initial segment dysfunction in epilepsy: Axon initial segment dysfunction in epilepsy
journal, May 2010
- Wimmer, Verena C.; Reid, Christopher A.; So, Eva Y. -W.
- The Journal of Physiology, Vol. 588, Issue 11
Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution
journal, November 2001
- Zhou, Yufeng; Morais-Cabral, João H.; Kaufman, Amelia
- Nature, Vol. 414, Issue 6859
Kv2 subunits underlie slowly inactivating potassium current in rat neocortical pyramidal neurons: Neocortical Kv2 channels
journal, June 2007
- Guan, D.; Tkatch, T.; Surmeier, D. J.
- The Journal of Physiology, Vol. 581, Issue 3
Dynamic localization and clustering of dendritic Kv2.1 voltage-dependent potassium channels in developing hippocampal neurons
journal, December 2001
- Antonucci, D. E.; Lim, S. T.; Vassanelli, S.
- Neuroscience, Vol. 108, Issue 1
The Role of Voltage-Gated Potassium Channels Kv2.1 and Kv2.2 in the Regulation of Insulin and Somatostatin Release from Pancreatic Islets
journal, November 2012
- Li, Xiaoyan (Nina); Herrington, James; Petrov, Aleksandr
- Journal of Pharmacology and Experimental Therapeutics, Vol. 344, Issue 2
KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy
journal, January 2012
- Weckhuysen, Sarah; Mandelstam, Simone; Suls, Arvid
- Annals of Neurology, Vol. 71, Issue 1
Regulation of ion channel localization and phosphorylation by neuronal activity
journal, June 2004
- Misonou, Hiroaki; Mohapatra, Durga P.; Park, Eunice W.
- Nature Neuroscience, Vol. 7, Issue 7
Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: a retrospective study
journal, August 2014
- Dyment, D. A.; Tétreault, M.; Beaulieu, C. L.
- Clinical Genetics, Vol. 88, Issue 1
Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units
journal, October 2012
- Saunders, C. J.; Miller, N. A.; Soden, S. E.
- Science Translational Medicine, Vol. 4, Issue 154
Dendrotoxin acceptor from bovine synaptic plasma membranes. Binding properties, purification and subunit composition of a putative constituent of certain voltage-activated K+ channels
journal, February 1989
- Parcej, D. N.; Dolly, J. O.
- Biochemical Journal, Vol. 257, Issue 3
Regulation of Kv2.1 K+ Conductance by Cell Surface Channel Density
journal, January 2013
- Fox, P. D.; Loftus, R. J.; Tamkun, M. M.
- Journal of Neuroscience, Vol. 33, Issue 3
Pharmacological chaperoning: A primer on mechanism and pharmacology
journal, May 2014
- Leidenheimer, Nancy J.; Ryder, Katelyn G.
- Pharmacological Research, Vol. 83
Clinical whole exome sequencing in child neurology practice: WES in Child Neurology
journal, August 2014
- Srivastava, Siddharth; Cohen, Julie S.; Vernon, Hilary
- Annals of Neurology, Vol. 76, Issue 4
Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel.
journal, December 1996
- Scannevin, R. H.; Murakoshi, H.; Rhodes, K. J.
- The Journal of Cell Biology, Vol. 135, Issue 6
The CARE Guidelines: Consensus-based Clinical Case Reporting Guideline Development
journal, September 2013
- Gagnier, Joel J.; Kienle, Gunver; Altman, Douglas G.
- Global Advances in Health and Medicine, Vol. 2, Issue 5
Differential transcriptional activation by Oct-1 and Oct-2: Interdependent activation domains induce Oct-2 phosphorylation
journal, February 1990
- Tanaka, Masafumi; Herr, Winship
- Cell, Vol. 60, Issue 3
Episodic ataxia results from voltage-dependent potassium channels with altered functions
journal, December 1995
- Adelman, John P.; Bond, Chris T.; Pessia, Mauro
- Neuron, Vol. 15, Issue 6
Genetics of early-onset epilepsy with encephalopathy
journal, January 2012
- Nabbout, Rima; Dulac, Olivier
- Nature Reviews Neurology, Vol. 8, Issue 3
Localization-dependent activity of the Kv2.1 delayed-rectifier K+ channel
journal, June 2010
- O'Connell, K. M. S.; Loftus, R.; Tamkun, M. M.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 27
Extending the KCNQ2 encephalopathy spectrum: Clinical and neuroimaging findings in 17 patients
journal, October 2013
- Weckhuysen, S.; Ivanovic, V.; Hendrickx, R.
- Neurology, Vol. 81, Issue 19
A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns
journal, January 1998
- Singh, Nanda A.; Charlier, Carole; Stauffer, Dora
- Nature Genetics, Vol. 18, Issue 1
A unique ion channel clustering domain on the axon initial segment of mammalian neurons: Ion channel clustering on the axon initial segment
journal, June 2014
- King, Anna N.; Manning, Colleen F.; Trimmer, James S.
- Journal of Comparative Neurology, Vol. 522, Issue 11
Identification of a trafficking determinant localized to the Kv1 potassium channel pore
journal, November 2001
- Manganas, L. N.; Wang, Q.; Scannevin, R. H.
- Proceedings of the National Academy of Sciences, Vol. 98, Issue 24
Polarized Axonal Surface Expression of Neuronal KCNQ Potassium Channels Is Regulated by Calmodulin Interaction with KCNQ2 Subunit
journal, July 2014
- Cavaretta, John P.; Sherer, Kaitlyn R.; Lee, Kwan Young
- PLoS ONE, Vol. 9, Issue 7
KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy
journal, January 2012
- Weckhuysen, Sarah; Mandelstam, Simone; Suls, Arvid
- Annals of Neurology, Vol. 71, Issue 1
Clinical whole exome sequencing in child neurology practice: WES in Child Neurology
journal, August 2014
- Srivastava, Siddharth; Cohen, Julie S.; Vernon, Hilary
- Annals of Neurology, Vol. 76, Issue 4
A unique ion channel clustering domain on the axon initial segment of mammalian neurons: Ion channel clustering on the axon initial segment
journal, June 2014
- King, Anna N.; Manning, Colleen F.; Trimmer, James S.
- Journal of Comparative Neurology, Vol. 522, Issue 11
Heterologous expression of the human potassium channel Kv2.1 in clonal mammalian cells by direct cytoplasmic microinjection of cRNA
journal, November 1992
- Ikeda, Stephen R.; Soler, Fernando; Z�hlke, Roger D.
- Pfl�gers Archiv European Journal of Physiology, Vol. 422, Issue 2
Differential transcriptional activation by Oct-1 and Oct-2: Interdependent activation domains induce Oct-2 phosphorylation
journal, February 1990
- Tanaka, Masafumi; Herr, Winship
- Cell, Vol. 60, Issue 3
A brefeldin A-like phenotype is induced by the overexpression of a human ERD-2-like protein, ELP-1
journal, May 1992
- Hsu, Victor W.; Shah, Nicky; Klausner, Richard D.
- Cell, Vol. 69, Issue 4
Episodic ataxia results from voltage-dependent potassium channels with altered functions
journal, December 1995
- Adelman, John P.; Bond, Chris T.; Pessia, Mauro
- Neuron, Vol. 15, Issue 6
De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies
journal, October 2014
- Appenzeller, Silke; Balling, Rudi; Barisic, Nina
- The American Journal of Human Genetics, Vol. 95, Issue 4
Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity
journal, January 2015
- Trimmer, James S.
- Neuron, Vol. 85, Issue 2
Pharmacological chaperoning: A primer on mechanism and pharmacology
journal, May 2014
- Leidenheimer, Nancy J.; Ryder, Katelyn G.
- Pharmacological Research, Vol. 83
Mutations in the K+ channel signature sequence
journal, April 1994
- Heginbotham, L.; Lu, Z.; Abramson, T.
- Biophysical Journal, Vol. 66, Issue 4
Inhibitory effects of pimozide on cloned and native voltage-gated potassium channels
journal, July 2003
- Zhang, Zhi-Hao; Lee, Yan T.; Rhodes, Kenneth
- Molecular Brain Research, Vol. 115, Issue 1
Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2
journal, April 2003
- Dedek, Karin; Fusco, Lucia; Teloy, Nicole
- Epilepsy Research, Vol. 54, Issue 1
Heteromultimeric channels formed by rat brain potassium-channel proteins
journal, June 1990
- Ruppersberg, J. Peter; Schröter, Klaus H.; Sakmann, Bert
- Nature, Vol. 345, Issue 6275
Determination of the subunit stoichiometry of a voltage-activated potassium channel
journal, March 1991
- MacKinnon, Roderick
- Nature, Vol. 350, Issue 6315
Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution
journal, November 2001
- Zhou, Yufeng; Morais-Cabral, João H.; Kaufman, Amelia
- Nature, Vol. 414, Issue 6859
Targeting F508del-CFTR to develop rational new therapies for cystic fibrosis
journal, June 2011
- Cai, Zhi-wei; Liu, Jia; Li, Hong-yu
- Acta Pharmacologica Sinica, Vol. 32, Issue 6
A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns
journal, January 1998
- Singh, Nanda A.; Charlier, Carole; Stauffer, Dora
- Nature Genetics, Vol. 18, Issue 1
A method and server for predicting damaging missense mutations
journal, April 2010
- Adzhubei, Ivan A.; Schmidt, Steffen; Peshkin, Leonid
- Nature Methods, Vol. 7, Issue 4
Regulation of ion channel localization and phosphorylation by neuronal activity
journal, June 2004
- Misonou, Hiroaki; Mohapatra, Durga P.; Park, Eunice W.
- Nature Neuroscience, Vol. 7, Issue 7
Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm
journal, June 2009
- Kumar, Prateek; Henikoff, Steven; Ng, Pauline C.
- Nature Protocols, Vol. 4, Issue 7
Interactions between lipids and voltage sensor paddles detected with tarantula toxins
journal, September 2009
- Milescu, Mirela; Bosmans, Frank; Lee, Seungkyu
- Nature Structural & Molecular Biology, Vol. 16, Issue 10
Dendrotoxin acceptor from bovine synaptic plasma membranes. Binding properties, purification and subunit composition of a putative constituent of certain voltage-activated K+ channels
journal, February 1989
- Parcej, D. N.; Dolly, J. O.
- Biochemical Journal, Vol. 257, Issue 3
Localization-dependent activity of the Kv2.1 delayed-rectifier K+ channel
journal, June 2010
- O'Connell, K. M. S.; Loftus, R.; Tamkun, M. M.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 27
Chemoselective tarantula toxins report voltage activation of wild-type ion channels in live cells
journal, October 2014
- Tilley, D. C.; Eum, K. S.; Fletcher-Taylor, S.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 44
Identification of a trafficking determinant localized to the Kv1 potassium channel pore
journal, November 2001
- Manganas, L. N.; Wang, Q.; Scannevin, R. H.
- Proceedings of the National Academy of Sciences, Vol. 98, Issue 24
Immunological identification and characterization of a delayed rectifier K+ channel polypeptide in rat brain.
journal, December 1991
- Trimmer, J. S.
- Proceedings of the National Academy of Sciences, Vol. 88, Issue 23
Subunit Composition Determines Kv1 Potassium Channel Surface Expression
journal, July 2000
- Manganas, Louis N.; Trimmer, James S.
- Journal of Biological Chemistry, Vol. 275, Issue 38
Potassium Channel Modulation by a Toxin Domain in Matrix Metalloprotease 23
journal, December 2009
- Rangaraju, Srikant; Khoo, Keith K.; Feng, Zhi-Ping
- Journal of Biological Chemistry, Vol. 285, Issue 12
Episodic Ataxia Type-1 Mutations in the Kv1.1 Potassium Channel Display Distinct Folding and Intracellular Trafficking Properties
journal, October 2001
- Manganas, Louis N.; Akhtar, Sobia; Antonucci, Dana E.
- Journal of Biological Chemistry, Vol. 276, Issue 52
Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding.
journal, January 1992
- Ridgway, N. D.; Dawson, P. A.; Ho, Y. K.
- Journal of Cell Biology, Vol. 116, Issue 2
Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel.
journal, December 1996
- Scannevin, R. H.; Murakoshi, H.; Rhodes, K. J.
- The Journal of Cell Biology, Vol. 135, Issue 6
Regulation of Kvl channel trafficking by the mamba snake neurotoxin dendrotoxin K
journal, December 2006
- Vacher, Helene; Mohapatra, Durga P.; Misonou, Hiroaki
- The FASEB Journal, Vol. 21, Issue 3
Rescue of Mutated Cardiac Ion Channels in Inherited Arrhythmia Syndromes
journal, January 2010
- Balijepalli, Sadguna Y.; Anderson, Corey L.; Lin, Eric C.
- Journal of Cardiovascular Pharmacology, Vol. 56, Issue 2
ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007
journal, April 2008
- Richards, C. Sue; Bale, Sherri; Bellissimo, Daniel B.
- Genetics in Medicine, Vol. 10, Issue 4
Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: a retrospective study
journal, August 2014
- Dyment, D. A.; Tétreault, M.; Beaulieu, C. L.
- Clinical Genetics, Vol. 88, Issue 1
Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability: Kv2.1 deletion and hyperexcitability
journal, March 2014
- Speca, D. J.; Ogata, G.; Mandikian, D.
- Genes, Brain and Behavior, Vol. 13, Issue 4
Frequency-dependent regulation of rat hippocampal somato-dendritic excitability by the K + channel subunit Kv2.1
journal, January 2000
- Du, Jing; Haak, Laurel L.; Phillips-Tansey, Emily
- The Journal of Physiology, Vol. 522, Issue 1
Axon initial segment dysfunction in epilepsy: Axon initial segment dysfunction in epilepsy
journal, May 2010
- Wimmer, Verena C.; Reid, Christopher A.; So, Eva Y. -W.
- The Journal of Physiology, Vol. 588, Issue 11
The Role of Voltage-Gated Potassium Channels Kv2.1 and Kv2.2 in the Regulation of Insulin and Somatostatin Release from Pancreatic Islets
journal, November 2012
- Li, Xiaoyan (Nina); Herrington, James; Petrov, Aleksandr
- Journal of Pharmacology and Experimental Therapeutics, Vol. 344, Issue 2
Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing
journal, January 2011
- Bell, C. J.; Dinwiddie, D. L.; Miller, N. A.
- Science Translational Medicine, Vol. 3, Issue 65
The CARE guidelines: consensus-based clinical case reporting guideline development
journal, October 2013
- Gagnier, J. J.; Kienle, G.; Altman, D. G.
- Case Reports, Vol. 2013, Issue oct23 1
Characterization of endogenous sodium channel gene expressed in Chinese hamster ovary cells
journal, April 1993
- Lalik, P. H.; Krafte, D. S.; Volberg, W. A.
- American Journal of Physiology-Cell Physiology, Vol. 264, Issue 4
The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ
journal, January 2008
- Sarmiere, Patrick D.; Weigle, Cecile M.; Tamkun, Michael M.
- BMC Neuroscience, Vol. 9, Issue 1
Extending the KCNQ2 encephalopathy spectrum: Clinical and neuroimaging findings in 17 patients
journal, October 2013
- Weckhuysen, S.; Ivanovic, V.; Hendrickx, R.
- Neurology, Vol. 81, Issue 19
Induction of stable ER-plasma-membrane junctions by Kv2.1 potassium channels
journal, April 2015
- Fox, P. D.; Haberkorn, C. J.; Akin, E. J.
- Journal of Cell Science, Vol. 128, Issue 11
Polarized Axonal Surface Expression of Neuronal KCNQ Potassium Channels Is Regulated by Calmodulin Interaction with KCNQ2 Subunit
journal, July 2014
- Cavaretta, John P.; Sherer, Kaitlyn R.; Lee, Kwan Young
- PLoS ONE, Vol. 9, Issue 7
Dynamic Regulation of the Kv2.1 Voltage-Gated Potassium Channel during Brain Ischemia through Neuroglial Interaction
journal, August 2008
- Misonou, H.; Thompson, S. M.; Cai, X.
- Journal of Neuroscience, Vol. 28, Issue 34
Identification of the Kv2.1 K + Channel as a Major Component of the Delayed Rectifier K + Current in Rat Hippocampal Neurons
journal, March 1999
- Murakoshi, Hideyuki; Trimmer, James S.
- The Journal of Neuroscience, Vol. 19, Issue 5
KCNQ2 Is a Nodal K+ Channel
journal, February 2004
- Devaux, J. J.
- Journal of Neuroscience, Vol. 24, Issue 5
The Kv2.1 C Terminus Can Autonomously Transfer Kv2.1-Like Phosphorylation-Dependent Localization, Voltage-Dependent Gating, and Muscarinic Modulation to Diverse Kv Channels
journal, January 2006
- Mohapatra, D. P.
- Journal of Neuroscience, Vol. 26, Issue 2
Blockers of the Delayed-Rectifier Potassium Current in Pancreatic -Cells Enhance Glucose-Dependent Insulin Secretion
journal, March 2006
- Herrington, J.; Zhou, Y. -P.; Bugianesi, R. M.
- Diabetes, Vol. 55, Issue 4
Works referencing / citing this record:
Precision physiology and rescue of brain ion channel disorders
journal, April 2017
- Noebels, Jeffrey
- The Journal of General Physiology, Vol. 149, Issue 5
Noncanonical Ion Channel Behaviour in Pain
journal, September 2019
- Ciotu, Cosmin I.; Tsantoulas, Christoforos; Meents, Jannis
- International Journal of Molecular Sciences, Vol. 20, Issue 18
Kv2.1 voltage‐gated potassium channels in developmental perspective
journal, September 2019
- Jędrychowska, Justyna; Korzh, Vladimir
- Developmental Dynamics, Vol. 248, Issue 12
Potassium Channel Gain of Function in Epilepsy: An Unresolved Paradox
journal, March 2018
- Niday, Zachary; Tzingounis, Anastasios V.
- The Neuroscientist, Vol. 24, Issue 4
Kv2 potassium channels form endoplasmic reticulum/plasma membrane junctions via interaction with VAPA and VAPB
journal, June 2018
- Johnson, Ben; Leek, Ashley N.; Solé, Laura
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 31
Models for discovery of targeted therapy in genetic epileptic encephalopathies
journal, September 2017
- Maljevic, Snezana; Reid, Christopher A.; Petrou, Steven
- Journal of Neurochemistry, Vol. 143, Issue 1
Spectrum of K V 2.1 Dysfunction in KCNB1 ‐Associated Neurodevelopmental Disorders
journal, October 2019
- Kang, Seok Kyu; Vanoye, Carlos G.; Misra, Sunita N.
- Annals of Neurology, Vol. 86, Issue 6
Monogenic disorders that mimic the phenotype of Rett syndrome
journal, January 2018
- Srivastava, Siddharth; Desai, Sonal; Cohen, Julie
- neurogenetics, Vol. 19, Issue 1
Identifying multi-hit carcinogenic gene combinations: Scaling up a weighted set cover algorithm using compressed binary matrix representation on a GPU
journal, February 2020
- Al Hajri, Qais; Dash, Sajal; Feng, Wu-chun
- Scientific Reports, Vol. 10, Issue 1
A molecular rheostat: Kv2.1 currents maintain or suppress repetitive firing in motoneurons
journal, June 2019
- Romer, Shannon H.; Deardorff, Adam S.; Fyffe, Robert E. W.
- The Journal of Physiology, Vol. 597, Issue 14
Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature
journal, September 2019
- Bar, Claire; Barcia, Giulia; Jennesson, Mélanie
- Human Mutation, Vol. 41, Issue 1
Oxidation of KCNB1 potassium channels triggers apoptotic integrin signaling in the brain
journal, April 2017
- Yu, Wei; Gowda, Manasa; Sharad, Yashsavi
- Cell Death & Disease, Vol. 8, Issue 4
Identifying multi-hit carcinogenic gene combinations: Scaling up a weighted set cover algorithm using compressed binary matrix representation on a GPU
journal, February 2020
- Al Hajri, Qais; Dash, Sajal; Feng, Wu-chun
- Scientific Reports, Vol. 10, Issue 1
Kv2 channels create endoplasmic reticulum / plasma membrane junctions: a brief history of Kv2 channel subcellular localization
journal, January 2019
- Johnson, Ben; Leek, Ashley N.; Tamkun, Michael M.
- Channels, Vol. 13, Issue 1
Noncanonical Ion Channel Behaviour in Pain
journal, September 2019
- Ciotu, Cosmin I.; Tsantoulas, Christoforos; Meents, Jannis
- International Journal of Molecular Sciences, Vol. 20, Issue 18