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Article
Joshua B. Holmes, Julian E. Stelzer
Danicamtiv and omecamtiv mecarbil are second- and first-generation myotropic sarcomere activators intended to treat patients with heart failure with reduced ejection fraction. This study directly compares the in vivo cardiac mechanisms to assess whether danicamtiv has improved upon the shortcomings of omecamtiv mecarbil.
Article
David Gong, Jennifer L. Orthmann-Murphy, Deepak Kumar, Gabriel D. Dungan, Ayman W. El-Hattab, Nicoline Schiess, Yun L. Luo, Mona M. Freidin, Charles K. Abrams
Gong et al. present two novel, disease-causing genetic variants of connexin 47. In vitro assays and MD simulations of these mutant proteins reveal unique mechanisms that relate connexin 47 mutations to severities of Pelizaeus–Merzbacher-like disease 1.
Article
Yu Zhou, Xiao-Ming Xia, Christopher J. Lingle
The role of BK S6 residues R329K330K331 and E321/E324 in β subunit–mediated inactivation is probed. WT R329K330K331 hinders inactivation in closed states, while RKK mutations stabilize inactivated states even under conditions where channels are otherwise closed. E321/E324 mutations do not permit closed-state inactivation.
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.
Journal of General Physiology Cover Image for Volume 157, Issue 3
Current Issue
Volume 157,
Issue 3,
5 May 2025
Reviews & Opinions
Research News | Contractile Function
Ben Short
JGP study reveals that glycerol storage increases the titin-based stiffness of muscle fibers, suggesting that this commonly used method should be avoided by researchers interested in the passive properties of muscle.
Viewpoint | Voltage-Gated Na Channels
Peter Hull, Angelika Lampert
Metaphors shape how we communicate and understand science, from genetic blueprints to molecular gates. This article explores their role in the sodium channel fast inactivation mechanism.
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.

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