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Article | Contractile Function
Josè Manuel Pioner, Enrico Pierantozzi, Raffaele Coppini, Egidio Maria Rubino, Valentina Biasci, Giulia Vitale, Annunziatina Laurino, Lorenzo Santini, Marina Scardigli, Davide Randazzo, Camilla Olianti, Matteo Serano, Daniela Rossi, Chiara Tesi, Elisabetta Cerbai, Stephan Lange, Carlo Reggiani, Leonardo Sacconi, Corrado Poggesi, Cecilia Ferrantini, Vincenzo Sorrentino
Obscurin deletion in mice is linked to compensated dilated cardiomyopathy, reduced sarcoplasmic reticulum volume, T-tubule alterations, altered E-C coupling, impaired response to inotropic agents, and increased propensity to arrhythmias.
Article | Contractile Function
Seong-Won Han, Justin Kolb, Gerrie P. Farman, Jochen Gohlke, Henk L. Granzier
To store and preserve muscle function, glycerol is often used, but its effect on passive properties is unclear. Muscles stored in glycerol showed increased passive stress that persisted after thin filament removal, indicating a titin-specific mechanism. Glycerol storage should be avoided in passive stiffness studies.
Article | Voltage-Gated Na Channels
Joseph L. Ransdell, Yarimar Carrasquillo, Marie K. Bosch, Rebecca L. Mellor, David M. Ornitz, Jeanne M. Nerbonne
FGF14 encodes a sodium channel accessory subunit. Mutations in Fgf14 are linked to spinocerebellar ataxia type 27. Fgf14 deletion in mouse Purkinje neurons causes reduced excitability. We show here that targeted Fgf14 deletion in mouse CA1 pyramidal neurons causes increased firing, revealing cell-type specific effects.
Article | Contractile Function
Eduardo Sánchez Díaz, Brayan Osegueda, Svetlana Minakhina, Nickolas Starks, Stefanie Novak, Dmitri Tolkatchev, Carol C. Gregorio, Alla S. Kostyukova, Garry E. Smith, Jr
In cardiac muscle, leiomodin-2 and tropomodulin-1 compete for binding thin filaments to control their length. We showed that mutations that lower leiomodin-2’s affinity for tropomyosin weaken its ability to displace tropomodulin-1. This highlights the critical role of the tropomyosin-binding site in the competition.
Article | Voltage-Gated Na Channels
Sooyeon Jo, Akie Fujita, Tomás Osorno, Robert G. Stewart, Patric M. Vaelli, Bruce P. Bean
Jo et al. use the Nav1.8 inhibitors suzetrigine, A-887826, and LTGO-33 to show differences in the kinetics with which the compounds unbind from depolarized channels and rebind to resting state channels, explaining reverse use dependence under physiological conditions seen with A-887826 but not suzetrigine or LTGO-33.
Article | Contractile Function
Kerry S. McDonald, Theodore J. Kalogeris, Adam B. Veteto, Daniel J. Davis, Laurin M. Hanft
McDonald et al. use permeabilized rodent left ventricular cardiac myocytes to study power generation during the ejection phase of the cardiac cycle. They show that cardiac myosin binding protein-C regulates sarcomere-loaded shortening, especially at high loads, seemingly, by modulating cross-bridge availability.
Article
Benjamin T. Simonson, Zhaoyang Jiang, Joseph F. Ryan, Timothy Jegla
Comb jellies are the oldest animal lineage and are missing six of our eight voltage-gated K+ channel lineages. We show here that they independently evolved a functionally diverse suite of voltage-gated K+ channels from a single ancestral Shaker family lineage.
Journal of General Physiology Cover Image for Volume 157, Issue 3
Current Issue
Volume 157,
Issue 3,
5 May 2025
Reviews & Opinions
Review | Voltage-Gated Na Channels
John N. Wood, Nieng Yan, Jian Huang, Jing Zhao, Armen Akopian, James J. Cox, C. Geoffrey Woods, Mohammed A. Nassar
The development of analgesic drugs targeting sodium channels NaV1.7 and NaV1.8 is described. FDA approval of the NaV1.8 antagonist suzetrigine presages an exciting new era in analgesic treatment with the drug alone, or in combination with other types of analgesic.
Research News
Ben Short
In a new JGP study, anatomically realistic simulations reveal how the complex architecture of rod synapses influences glutamate dynamics and postsynaptic responses.
Commentary
Lawrence Salkoff
Studies of potassium channel evolution from the Jegla group contribute valuable insights into the evolution of complexity in electrical signaling and the conservation and repurposing of key molecular components throughout evolutionary history.

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