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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.
Communication | Contractile Function
Dalma Kellermayer, Cristina M. Șulea, Hedvig Tordai, Kálmán Benke, Miklós Pólos, Bence Ágg, Roland Stengl, Máté Csonka, Tamás Radovits, Béla Merkely, Zoltán Szabolcs, Miklós Kellermayer, Balázs Kiss
Intrinsic cardiomyopathy is an emerging cause of heart failure in Marfan syndrome. Kellermayer et al. show that the ratio between titin isoforms N2BA and N2B is biased toward N2BA, suggesting an adaptation mechanism to counter passive-stiffness changes manifested in the Marfan syndrome cardiac tissue.
Article
Lucian Medrihan, Margarete G. Knudsen, Tatiana Ferraro, Pedro Del Cioppo Vasques, Yevgeniy Romin, Sho Fujisawa, Paul Greengard, Ana Milosevic
Cholinergic interneurons of the nucleus accumbens have a critical role regulating depressive-like behavior. Medrihan et al. use monosynaptic cell tracing in a depression mouse model to determine the regions projecting to the nucleus accumbens’ cholinergic neurons and to show that projections from the ventral hippocampus were significantly reduced in depressed mice.
Article
Morris Vysma, James S. Welsh, Derek R. Laver
Vysma et al. develop a Ca2+ release model that reproduces store load–dependent release and Ca2+ waves in skinned ventricular myocytes. They find that substantial increases in SR Ca2+ release and Ca2+ waves take place when Ca2+ sparks become prolonged embers above a threshold SR [Ca2+].
Journal of General Physiology Cover Image for Volume 157, Issue 2
Current Issue
Volume 157,
Issue 2,
3 March 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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