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  1. Article ; Online: Voltage gated sodium and calcium channels: Discovery, structure, function, and Pharmacology.

    Catterall, William A

    Channels (Austin, Tex.)

    2023  Volume 17, Issue 1, Page(s) 2281714

    Abstract: Voltage-gated sodium channels initiate action potentials in nerve and muscle, and voltage-gated calcium channels couple depolarization of the plasma membrane to intracellular events such as secretion, contraction, synaptic transmission, and gene ... ...

    Abstract Voltage-gated sodium channels initiate action potentials in nerve and muscle, and voltage-gated calcium channels couple depolarization of the plasma membrane to intracellular events such as secretion, contraction, synaptic transmission, and gene expression. In this Review and Perspective article, I summarize early work that led to identification, purification, functional reconstitution, and determination of the amino acid sequence of the protein subunits of sodium and calcium channels and showed that their pore-forming subunits are closely related. Decades of study by antibody mapping, site-directed mutagenesis, and electrophysiological recording led to detailed two-dimensional structure-function maps of the amino acid residues involved in voltage-dependent activation and inactivation, ion permeation and selectivity, and pharmacological modulation. Most recently, high-resolution three-dimensional structure determination by X-ray crystallography and cryogenic electron microscopy has revealed the structural basis for sodium and calcium channel function and pharmacological modulation at the atomic level. These studies now define the chemical basis for electrical signaling and provide templates for future development of new therapeutic agents for a range of neurological and cardiovascular diseases.
    MeSH term(s) Calcium Channels/metabolism ; Sodium/metabolism ; Voltage-Gated Sodium Channels/metabolism ; Amino Acid Sequence ; Action Potentials ; Calcium/metabolism
    Chemical Substances Calcium Channels ; Sodium (9NEZ333N27) ; Voltage-Gated Sodium Channels ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2023-11-20
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2262854-X
    ISSN 1933-6969 ; 1933-6969
    ISSN (online) 1933-6969
    ISSN 1933-6969
    DOI 10.1080/19336950.2023.2281714
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  2. Article ; Online: Synaptotagmin-7 Enhances Facilitation of Ca

    Djillani, Alaeddine / Bazinet, Jeremy / Catterall, William A

    eNeuro

    2022  Volume 9, Issue 3

    Abstract: Voltage-gated calcium channel ... ...

    Abstract Voltage-gated calcium channel Ca
    MeSH term(s) Calcium/metabolism ; Calcium Channels, N-Type/metabolism ; Neuronal Plasticity/physiology ; Presynaptic Terminals/metabolism ; Synaptic Transmission ; Synaptotagmins/genetics ; Synaptotagmins/metabolism
    Chemical Substances Calcium Channels, N-Type ; voltage-dependent calcium channel (P-Q type) ; Synaptotagmins (134193-27-4) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2022-05-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0081-22.2022
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  3. Article ; Online: Cell-cycle arrest at the G1/S boundary enhances transient voltage-gated ion channel expression in human and insect cells.

    Eltokhi, Ahmed / Catterall, William A / Gamal El-Din, Tamer M

    Cell reports methods

    2023  Volume 3, Issue 9, Page(s) 100559

    Abstract: Heterologous expression of recombinant ion channel subunits in cell lines is often limited by the presence of a low number of channels at the cell surface level. Here, we introduce a combination of two techniques: viral expression using the baculovirus ... ...

    Abstract Heterologous expression of recombinant ion channel subunits in cell lines is often limited by the presence of a low number of channels at the cell surface level. Here, we introduce a combination of two techniques: viral expression using the baculovirus system plus cell-cycle arrest at the G1/S boundary using either thymidine or hydroxyurea. This method achieved a manifold increase in the peak current density of expressed ion channels compared with the classical liposome-mediated transfection methods. The enhanced ionic current was accompanied by an increase in the density of gating charges, confirming that the increased yield of protein and ionic current reflects the functional localization of channels in the plasma membrane. This modified method of viral expression coordinated with the cell cycle arrest will pave the way to better decipher the structure and function of ion channels and their association with ion channelopathies.
    MeSH term(s) Humans ; Ion Channel Gating ; Ion Channels/genetics ; Cell Membrane/metabolism ; Transfection ; Cell Cycle Checkpoints/genetics
    Chemical Substances Ion Channels
    Language English
    Publishing date 2023-08-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2667-2375
    ISSN (online) 2667-2375
    DOI 10.1016/j.crmeth.2023.100559
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  4. Article ; Online: Dravet Syndrome: A Sodium Channel Interneuronopathy.

    Catterall, William A

    Current opinion in physiology

    2017  Volume 2, Page(s) 42–50

    Abstract: Dravet Syndrome is a devastating childhood epilepsy disorder with high incidence of premature death plus comorbidities of ataxia, circadian rhythm disorder, impaired sleep quality, autistic-like social-interaction deficits and severe cognitive impairment. ...

    Abstract Dravet Syndrome is a devastating childhood epilepsy disorder with high incidence of premature death plus comorbidities of ataxia, circadian rhythm disorder, impaired sleep quality, autistic-like social-interaction deficits and severe cognitive impairment. It is primarily caused by heterozygous loss-of-function mutations in the
    Language English
    Publishing date 2017-12-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2918626-2
    ISSN 2468-8673 ; 2468-8681
    ISSN (online) 2468-8673
    ISSN 2468-8681
    DOI 10.1016/j.cophys.2017.12.007
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  5. Article ; Online: Forty Years of Sodium Channels: Structure, Function, Pharmacology, and Epilepsy.

    Catterall, William A

    Neurochemical research

    2017  Volume 42, Issue 9, Page(s) 2495–2504

    Abstract: Voltage-gated sodium channels initiate action potentials in brain neurons. In the 1970s, much was known about the function of sodium channels from measurements of ionic currents using the voltage clamp method, but there was no information about the ... ...

    Abstract Voltage-gated sodium channels initiate action potentials in brain neurons. In the 1970s, much was known about the function of sodium channels from measurements of ionic currents using the voltage clamp method, but there was no information about the sodium channel molecules themselves. As a postdoctoral fellow and staff scientist at the National Institutes of Health, I developed neurotoxins as molecular probes of sodium channels in cultured neuroblastoma cells. During those years, Bruce Ransom and I crossed paths as members of the laboratories of Marshall Nirenberg and Philip Nelson and shared insights about sodium channels in neuroblastoma cells from my work and electrical excitability and synaptic transmission in cultured spinal cord neurons from Bruce's pioneering electrophysiological studies. When I established my laboratory at the University of Washington in 1977, my colleagues and I used those neurotoxins to identify the protein subunits of sodium channels, purify them, and reconstitute their ion conductance activity in pure form. Subsequent studies identified the molecular basis for the main functions of sodium channels-voltage-dependent activation, rapid and selective ion conductance, and fast inactivation. Bruce Ransom and I re-connected in the 1990s, as ski buddies at the Winter Conference on Brain Research and as faculty colleagues at the University of Washington when Bruce became our founding Chair of Neurology and provided visionary leadership of that department. In the past decade my work on sodium channels has evolved into structural biology. Molecular modeling and X-ray crystallographic studies have given new views of sodium channel function at atomic resolution. Sodium channels are also the molecular targets for genetic diseases, including Dravet Syndrome, an intractable pediatric epilepsy disorder with major co-morbidities of cognitive deficit, autistic-like behaviors, and premature death that is caused by loss-of-function mutations in the brain sodium channel Na
    MeSH term(s) Action Potentials/drug effects ; Action Potentials/physiology ; Animals ; Epilepsy/metabolism ; Humans ; Ion Channel Gating/drug effects ; Ion Channel Gating/physiology ; Neurotoxins/metabolism ; Neurotoxins/pharmacology ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Protein Subunits/physiology ; Sodium Channels/chemistry ; Sodium Channels/physiology
    Chemical Substances Neurotoxins ; Protein Subunits ; Sodium Channels
    Language English
    Publishing date 2017-06-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 199335-5
    ISSN 1573-6903 ; 0364-3190
    ISSN (online) 1573-6903
    ISSN 0364-3190
    DOI 10.1007/s11064-017-2314-9
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  6. Article: Impairment of β-adrenergic regulation and exacerbation of pressure-induced heart failure in mice with mutations in phosphoregulatory sites in the cardiac Ca

    Hovey, Liam / Guo, Xiaoyun / Chen, Yi / Liu, Qinghang / Catterall, William A

    Frontiers in physiology

    2023  Volume 14, Page(s) 1049611

    Abstract: The cardiac calcium channel ... ...

    Abstract The cardiac calcium channel Ca
    Language English
    Publishing date 2023-02-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1049611
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  7. Article ; Online: Pathogenic gating pore current conducted by autism-related mutations in the Na

    Eltokhi, Ahmed / Lundstrom, Brian Nils / Li, Jin / Zweifel, Larry S / Catterall, William A / Gamal El-Din, Tamer M

    Proceedings of the National Academy of Sciences of the United States of America

    2024  Volume 121, Issue 15, Page(s) e2317769121

    Abstract: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social and communication deficits and repetitive behaviors. The genetic heterogeneity of ASD presents a challenge to the development of an effective treatment ... ...

    Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social and communication deficits and repetitive behaviors. The genetic heterogeneity of ASD presents a challenge to the development of an effective treatment targeting the underlying molecular defects. ASD gating charge mutations in the
    MeSH term(s) Humans ; Autism Spectrum Disorder/genetics ; Autistic Disorder/genetics ; Brain ; Mutation ; Voltage-Gated Sodium Channels
    Chemical Substances Voltage-Gated Sodium Channels ; SCN2A protein, human
    Language English
    Publishing date 2024-04-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2317769121
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    Zs.A 1148: Show issues Location:
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  8. Article ; Online: Structural basis for severe pain caused by mutations in the S4-S5 linkers of voltage-gated sodium channel Na

    Wisedchaisri, Goragot / Gamal El-Din, Tamer M / Zheng, Ning / Catterall, William A

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 14, Page(s) e2219624120

    Abstract: Gain-of-function mutations in voltage-gated sodium channel ... ...

    Abstract Gain-of-function mutations in voltage-gated sodium channel Na
    MeSH term(s) Humans ; NAV1.7 Voltage-Gated Sodium Channel/genetics ; NAV1.7 Voltage-Gated Sodium Channel/metabolism ; Pain/genetics ; Pain/metabolism ; Mutation ; Erythromelalgia/genetics ; Erythromelalgia/metabolism ; Erythromelalgia/pathology ; Voltage-Gated Sodium Channels/genetics ; Threonine/genetics
    Chemical Substances NAV1.7 Voltage-Gated Sodium Channel ; Voltage-Gated Sodium Channels ; Threonine (2ZD004190S)
    Language English
    Publishing date 2023-03-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2219624120
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    Zs.A 1148: Show issues Location:
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  9. Article ; Online: Convergent regulation of Ca

    Hovey, Liam / Gamal El-Din, Tamer M / Catterall, William A

    Proceedings of the National Academy of Sciences of the United States of America

    2022  Volume 119, Issue 42, Page(s) e2208533119

    Abstract: The L-type calcium currents conducted by the cardiac ... ...

    Abstract The L-type calcium currents conducted by the cardiac Ca
    MeSH term(s) Adrenergic Agents ; Calcium/metabolism ; Calcium Channels, L-Type/metabolism ; Cyclic AMP-Dependent Protein Kinases/genetics ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Guanosine/metabolism ; Monomeric GTP-Binding Proteins/metabolism ; Phosphorylation
    Chemical Substances Adrenergic Agents ; Calcium Channels, L-Type ; Guanosine (12133JR80S) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Monomeric GTP-Binding Proteins (EC 3.6.5.2) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2022-10-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2208533119
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  10. Article ; Online: Finding Channels.

    Catterall, William A

    The Journal of biological chemistry

    2015  Volume 290, Issue 47, Page(s) 28357–28373

    MeSH term(s) Ion Channels/chemistry ; Ion Channels/physiology ; Molecular Probes ; Photoaffinity Labels ; Structure-Activity Relationship
    Chemical Substances Ion Channels ; Molecular Probes ; Photoaffinity Labels
    Language English
    Publishing date 2015-10-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.X115.683383
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