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Samira Yazdi, Johan Nikesjö, Williams Miranda, Valentina Corradi, D. Peter Tieleman, Sergei Yu. Noskov, H. Peter Larsson, Sara I. Liin
The cardiac KCNQ1 channel is a promising anti-arrhythmic target. Yazdi et al. report on how PUFAs interact with two binding sites in KCNQ1 to trigger channel activation. These findings further our mechanistic understanding of how to modulate KCNQ1 activity.
Beatrice Scellini, Nicoletta Piroddi, Marica Dente, Giulia Vitale, Josè Manuel Pioner, Raffaele Coppini, Cecilia Ferrantini, Corrado Poggesi, Chiara Tesi
Scellini et al. show that mavacamten, a preclinical inhibitor of sarcomeric myosins, has a fast and reversible mechanical action on skeletal and cardiac myofibers that is mediated by a shift of motor heads out of a force-generating cycle, with no effect on the kinetics of cardiac force development.
David V. Rasicci, Orville Kirkland, Jr., Faruk H. Moonschi, Neil B. Wood, Danuta Szczesna-Cordary, Michael J. Previs, Jonathan F. Wenk, Kenneth S. Campbell, Christopher M. Yengo
Rasicci et al. investigate the mechanochemical properties of distinct isoforms of cardiac myosin carrying the K104E regulatory light chain mutation, previously associated with hypertrophic cardiomyopathy. They demonstrate that the mutation does not affect the ATPase or motor properties of human cardiac myosin subfragment-1 (M2β-S1), but the mutation increases the sliding velocity and disrupts RLC incorporation in full-length α-cardiac myosin.
Sarah R. Clippinger, Paige E. Cloonan, Wei Wang, Lina Greenberg, W. Tom Stump, Paweorn Angsutararux, Jeanne M. Nerbonne, Michael J. Greenberg
Clippinger et al. examine a mutation in troponin T that causes hypertrophic cardiomyopathy and demonstrate that increased molecular mechanics drive the early disease pathogenesis, leading to secondary activation of mechanobiological signaling pathways.
Zhuyuan Chen, Georg Kuenze, Jens Meiler, Cecilia M. Canessa
Acid-sensing ion channels (ASIC) play central roles in the central and peripheral nervous systems. In this paper, Chen et al. show that changes to a single arginine of a human ASIC both affect the efficacy of proton-mediated gating and delay the desensitization of the channel.
Farbod Fazlollahi, Jorge J. Santini Gonzalez, Steven J. Repas, Benjamin D. Canan, George E. Billman, Paul M.L. Janssen
Fazlollahi et al. show that contraction and relaxation remain tightly coupled in intact canine myocardium after exercise training and/or myocardial infarction. They postulate that the action of cardiac myosin binding protein C on actin and myosin may play a key role in this process.
Chiara Stronczek, Stephan Lange, Belinda Bullard, Sebastian Wolniak, Emma Börgeson, Olga Mayans, Jennifer R. Fleming
Stronczek et al. analyze the structure of the titin-N2A poly-Ig segment, a key signaling element in the sarcomere. They reveal a unique topography for the I81-I83 tandem, but they could not confirm the presence of Ca2+ binding sites in I81-I83 or the interaction of N2A with actin.

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Volume 153,
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