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  1. Article ; Online: Controlling the Traffic to Keep the Beat: Targeting of Myocardial Sodium Channels.

    Nerbonne, Jeanne M

    Circulation research

    2021  Volume 129, Issue 3, Page(s) 366–368

    MeSH term(s) Myocardium ; Sodium Channels
    Chemical Substances Sodium Channels
    Language English
    Publishing date 2021-07-22
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.121.319653
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  2. Article ; Online: Effects of NALCN-Encoded Na

    Yang, Nien-Du / Mellor, Rebecca L / Hermanstyne, Tracey O / Nerbonne, Jeanne M

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2023  Volume 43, Issue 28, Page(s) 5132–5141

    Abstract: Neurons in the suprachiasmatic nucleus (SCN) generate circadian changes in the rates of spontaneous action potential firing that regulate and synchronize daily rhythms in physiology and behavior. Considerable evidence suggests that daily rhythms in the ... ...

    Abstract Neurons in the suprachiasmatic nucleus (SCN) generate circadian changes in the rates of spontaneous action potential firing that regulate and synchronize daily rhythms in physiology and behavior. Considerable evidence suggests that daily rhythms in the repetitive firing rates (higher during the day than at night) of SCN neurons are mediated by changes in subthreshold potassium (K
    MeSH term(s) Mice ; Male ; Female ; Animals ; Suprachiasmatic Nucleus Neurons ; Membrane Potentials/physiology ; Action Potentials/physiology ; Circadian Rhythm/physiology ; Neurons/physiology ; Suprachiasmatic Nucleus/physiology ; Mammals ; Ion Channels ; Membrane Proteins
    Chemical Substances NALCN protein, mouse ; Ion Channels ; Membrane Proteins
    Language English
    Publishing date 2023-06-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.0182-23.2023
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  3. Article ; Online: Molecular Basis of Functional Myocardial Potassium Channel Diversity.

    Nerbonne, Jeanne M

    Cardiac electrophysiology clinics

    2016  Volume 8, Issue 2, Page(s) 257–273

    Abstract: Multiple types of voltage-gated K(+) and non-voltage-gated K(+) currents have been distinguished in mammalian cardiac myocytes based on differences in time-dependent and voltage-dependent properties and pharmacologic sensitivities. Many of the genes ... ...

    Abstract Multiple types of voltage-gated K(+) and non-voltage-gated K(+) currents have been distinguished in mammalian cardiac myocytes based on differences in time-dependent and voltage-dependent properties and pharmacologic sensitivities. Many of the genes encoding voltage-gated K(+) (Kv) and non-voltage-gated K(+) (Kir and K2P) channel pore-forming and accessory subunits are expressed in the heart, and a variety of approaches have been, and continue to be, used to define the molecular determinants of native cardiac K(+) channels and to explore the molecular mechanisms controlling the diversity, regulation, and remodeling of these channels in the normal and diseased myocardium.
    MeSH term(s) Action Potentials ; Animals ; Delayed Rectifier Potassium Channels/metabolism ; Delayed Rectifier Potassium Channels/physiology ; Delayed Rectifier Potassium Channels/ultrastructure ; Humans ; Mice ; Myocardium/cytology ; Myocardium/ultrastructure ; Myocytes, Cardiac ; Protein Subunits ; Rats
    Chemical Substances Delayed Rectifier Potassium Channels ; Protein Subunits
    Language English
    Publishing date 2016-06
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1877-9190
    ISSN (online) 1877-9190
    DOI 10.1016/j.ccep.2016.01.001
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  4. Article: Kv12-Encoded K

    Hermanstyne, Tracey O / Yang, Nien-Du / Granados-Fuentes, Daniel / Li, Xiaofan / Mellor, Rebecca L / Jegla, Timothy / Herzog, Erik D / Nerbonne, Jeanne M

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium ( ... ...

    Abstract Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K
    Language English
    Publishing date 2023-02-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.30.526323
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  5. Article ; Online: Mouse models of arrhythmogenic cardiovascular disease: challenges and opportunities.

    Nerbonne, Jeanne M

    Current opinion in pharmacology

    2014  Volume 15, Page(s) 107–114

    Abstract: Arrhythmogenic cardiovascular disease is associated with significant morbidity and mortality and, in spite of therapeutic advances, remains an enormous public health burden. The scope of this problem motivates efforts to delineate the molecular, cellular ...

    Abstract Arrhythmogenic cardiovascular disease is associated with significant morbidity and mortality and, in spite of therapeutic advances, remains an enormous public health burden. The scope of this problem motivates efforts to delineate the molecular, cellular and systemic mechanisms underlying increased arrhythmia risk in inherited and acquired cardiac and systemic disease. The mouse is used increasingly in these efforts owing to the ease with which genetic strategies can be exploited and mechanisms can be probed. The question then arises whether the mouse has proven to be a useful model system to delineate arrhythmogenic cardiovascular disease mechanisms. Rather than trying to provide a definite answer, the goal here is to consider the issues that arise when using mouse models and to highlight the opportunities.
    MeSH term(s) Animals ; Arrhythmias, Cardiac/physiopathology ; Disease Models, Animal ; Humans ; Mice
    Language English
    Publishing date 2014-03-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2037057-X
    ISSN 1471-4973 ; 1471-4892
    ISSN (online) 1471-4973
    ISSN 1471-4892
    DOI 10.1016/j.coph.2014.02.003
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  6. Article ; Online: Intrinsic mechanisms in the gating of resurgent Na

    Ransdell, Joseph L / Moreno, Jonathan D / Bhagavan, Druv / Silva, Jonathan R / Nerbonne, Jeanne M

    eLife

    2022  Volume 11

    Abstract: The resurgent component of the voltage-gated sodium current ( ... ...

    Abstract The resurgent component of the voltage-gated sodium current (I
    MeSH term(s) Action Potentials/physiology ; Animals ; Animals, Newborn ; Cerebellum/cytology ; Female ; Ion Channel Gating ; Kinetics ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/cytology ; Neurons/metabolism ; Patch-Clamp Techniques ; Postural Balance/physiology ; Purkinje Cells/metabolism ; Sodium/metabolism ; Voltage-Gated Sodium Channel beta-4 Subunit/deficiency ; Voltage-Gated Sodium Channel beta-4 Subunit/metabolism
    Chemical Substances Scn4b protein, mouse ; Voltage-Gated Sodium Channel beta-4 Subunit ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2022-01-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.70173
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  7. Article ; Online: Voltage-gated sodium currents in cerebellar Purkinje neurons: functional and molecular diversity.

    Ransdell, Joseph L / Nerbonne, Jeanne M

    Cellular and molecular life sciences : CMLS

    2018  Volume 75, Issue 19, Page(s) 3495–3505

    Abstract: Purkinje neurons, the sole output of the cerebellar cortex, deliver GABA-mediated inhibition to the deep cerebellar nuclei. To subserve this critical function, Purkinje neurons fire repetitively, and at high frequencies, features that have been linked to ...

    Abstract Purkinje neurons, the sole output of the cerebellar cortex, deliver GABA-mediated inhibition to the deep cerebellar nuclei. To subserve this critical function, Purkinje neurons fire repetitively, and at high frequencies, features that have been linked to the unique properties of the voltage-gated sodium (Nav) channels expressed. In addition to the rapidly activating and inactivating, or transient, component of the Nav current (I
    MeSH term(s) Action Potentials/genetics ; Action Potentials/physiology ; Animals ; Cerebellum/cytology ; Cerebellum/physiology ; Humans ; Ion Channel Gating/genetics ; Ion Channel Gating/physiology ; Neurons/metabolism ; Neurons/physiology ; Purkinje Cells/cytology ; Purkinje Cells/physiology ; Voltage-Gated Sodium Channels/classification ; Voltage-Gated Sodium Channels/genetics ; Voltage-Gated Sodium Channels/physiology
    Chemical Substances Voltage-Gated Sodium Channels
    Language English
    Publishing date 2018-07-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-018-2868-y
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    Zs.A 195: Show issues Location:
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  8. Article ; Online: Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors.

    Angsutararux, Paweorn / Dutta, Amal K / Marras, Martina / Abella, Carlota / Mellor, Rebecca L / Shi, Jingyi / Nerbonne, Jeanne M / Silva, Jonathan R

    The Journal of general physiology

    2023  Volume 155, Issue 5

    Abstract: Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple ... ...

    Abstract Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple accessory proteins, including intracellular fibroblast growth factors (iFGF). In spite of high homology, each of the iFGFs, iFGF11-iFGF14, as well as the individual iFGF splice variants, differentially regulates NaV channel gating, and the mechanisms underlying these differential effects remain elusive. Much of the work exploring iFGF regulation of NaV1.5 has been performed in mouse and rat ventricular myocytes in which iFGF13VY is the predominant iFGF expressed, whereas investigation into NaV1.5 regulation by the human heart-dominant iFGF12B is lacking. In this study, we used a mouse model with cardiac-specific Fgf13 deletion to study the consequences of iFGF13VY and iFGF12B expression. We observed distinct effects on the voltage-dependences of activation and inactivation of the sodium currents (INa), as well as on the kinetics of peak INa decay. Results in native myocytes were recapitulated with human NaV1.5 heterologously expressed in Xenopus oocytes, and additional experiments using voltage-clamp fluorometry (VCF) revealed iFGF-specific effects on the activation of the NaV1.5 voltage sensor domain in repeat IV (VSD-IV). iFGF chimeras further unveiled roles for all three iFGF domains (i.e., the N-terminus, core, and C-terminus) on the regulation of VSD-IV, and a slower time domain of inactivation. We present here a novel mechanism of iFGF regulation that is specific to individual iFGF isoforms and that leads to distinct functional effects on NaV channel/current kinetics.
    MeSH term(s) Mice ; Rats ; Humans ; Animals ; Sodium Channels/metabolism ; Action Potentials/physiology ; Protein Isoforms/metabolism ; Myocytes, Cardiac/metabolism ; Fibroblast Growth Factors/genetics ; Fibroblast Growth Factors/metabolism
    Chemical Substances Sodium Channels ; Protein Isoforms ; Fibroblast Growth Factors (62031-54-3)
    Language English
    Publishing date 2023-03-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 3118-5
    ISSN 1540-7748 ; 0022-1295
    ISSN (online) 1540-7748
    ISSN 0022-1295
    DOI 10.1085/jgp.202213300
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  9. Article ; Online: Kv12-encoded K+ channels drive the day-night switch in the repetitive firing rates of SCN neurons.

    Hermanstyne, Tracey O / Yang, Nien-Du / Granados-Fuentes, Daniel / Li, Xiaofan / Mellor, Rebecca L / Jegla, Timothy / Herzog, Erik D / Nerbonne, Jeanne M

    The Journal of general physiology

    2023  Volume 155, Issue 9

    Abstract: Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K+) channels regulate daily oscillations in the spontaneous firing rates of neurons in the suprachiasmatic nucleus (SCN), the master circadian ... ...

    Abstract Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K+) channels regulate daily oscillations in the spontaneous firing rates of neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals. The K+ conductance(s) driving these daily rhythms in the repetitive firing rates of SCN neurons, however, have not been identified. To test the hypothesis that subthreshold Kv12.1/Kv12.2-encoded K+ channels play a role, we obtained current-clamp recordings from SCN neurons in slices prepared from adult mice harboring targeted disruptions in the Kcnh8 (Kv12.1-/-) or Kcnh3 (Kv12.2-/-) locus. We found that mean nighttime repetitive firing rates were higher in Kv12.1-/- and Kv12.2-/- than in wild type (WT), SCN neurons. In marked contrast, mean daytime repetitive firing rates were similar in Kv12.1-/-, Kv12.2-/-, and WT SCN neurons, and the day-night difference in mean repetitive firing rates, a hallmark feature of WT SCN neurons, was eliminated in Kv12.1-/- and Kv12.2-/- SCN neurons. Similar results were obtained with in vivo shRNA-mediated acute knockdown of Kv12.1 or Kv12.2 in adult SCN neurons. Voltage-clamp experiments revealed that Kv12-encoded current densities in WT SCN neurons are higher at night than during the day. In addition, the pharmacological block of Kv12-encoded currents increased the mean repetitive firing rate of nighttime, but not daytime, in WT SCN neurons. Dynamic clamp-mediated subtraction of modeled Kv12-encoded currents also selectively increased the mean repetitive firing rates of nighttime WT SCN neurons. Despite the elimination of the nighttime decrease in the mean repetitive firing rates of SCN neurons, however, locomotor (wheel-running) activity remained rhythmic in Kv12.1-/-, Kv12.2-/-, and Kv12.1-targeted shRNA-expressing, and Kv12.2-targeted shRNA-expressing animals.
    MeSH term(s) Animals ; Mice ; Mammals ; Neurons ; Potassium ; RNA, Small Interfering ; Suprachiasmatic Nucleus ; Suprachiasmatic Nucleus Neurons
    Chemical Substances Potassium (RWP5GA015D) ; RNA, Small Interfering ; Kv12.1 potassium channel, mouse ; Kcnh3 protein, mouse
    Language English
    Publishing date 2023-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3118-5
    ISSN 1540-7748 ; 0022-1295
    ISSN (online) 1540-7748
    ISSN 0022-1295
    DOI 10.1085/jgp.202213310
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  10. Article ; Online: Training the Next Generation of Translational Cardiovascular Investigators: Is the Pipeline Half Full or Half Empty?

    Nerbonne, Jeanne M / Mann, Douglas L

    JACC. Basic to translational science

    2016  Volume 1, Issue 6, Page(s) 554–556

    Language English
    Publishing date 2016-10-31
    Publishing country United States
    Document type Editorial
    ISSN 2452-302X
    ISSN (online) 2452-302X
    DOI 10.1016/j.jacbts.2016.08.003
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