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Article | Voltage-Gated Na Channels
Elaine Tao, Ben Corry
Tao and Corry investigate how the binding of sodium channel inhibitors to the Nav1.5 pore using simulations reveal promiscuous, polyspecific binding at the fenestrations and central cavity. These findings shed light on diverse ways drugs inhibit the channel, offering insights for improving therapeutic development for conditions like chronic pain, epilepsy, and cardiac arrhythmias.
Methods and Approaches
Alessandra Picollo, Michael Pusch
Picollo and Pusch present ALLIN (Annotation of sequence aLignment and structuraL ProteIn visualizatioN), a web interface to generate an interactive HTML page for the simultaneous visualization of annotated protein sequences alignment and 3-D structures or homology models of the related proteins.
Article
Sabrina I. Apel, Emily Schaffter, Nicholas Melisi, Matthew J. Gage
Apel et al. demonstrate that the calcium-binding protein S100A1 binds the N2A region of titin and that binding is regulated through calcium concentration and pH. Their work suggests that this interaction is a physiological sensor to regulate titin function in the muscle.
Article
Jonathan Schreiber, Ludivine Rotard, Yves Tourneur, Aude Lafoux, Christine Berthier, Bruno Allard, Corinne Huchet, Vincent Jacquemond
Defective Ca2+ signaling in muscle cells is thought to play a role in Duchenne muscular dystrophy. Schreiber et al. report that voltage-activated SR Ca2+ release is moderately depressed in muscle fibers isolated from a rat model that reproduces the human disease well.
Article
Smriti Gupta, Yu-Hsin Chiu, Mohan C. Manjegowda, Bimal N. Desai, Kodi S. Ravichandran, Douglas A. Bayliss
Gupta et al. show that Pannexin 1 (PANX1) channels can function as both hexamers and heptamers, but that heptameric PANX1 shows higher conductance, longer mean open times, and supports greater ATP release and dye uptake. Structurally distinct mechanisms underlie C-tail cleavage and receptor-mediated PANX1 activation.
Article | Pain Focus
Lisa A. McIlvried, John Smith Del Rosario, Melanie Y. Pullen, Andi Wangzhou, Tayler D. Sheahan, Andrew J. Shepherd, Richard A. Slivicki, John A. Lemen, Theodore J. Price, Bryan A. Copits, Robert W. Gereau, IV
In this study, McIlvried, Del Rosario, and colleagues show that mechanisms of adaptive plasticity are engaged in mouse and human sensory neurons after sustained depolarization. This phenomenon is reversible and involves alterations of voltage-gated sodium channel currents.
Hypothesis | Voltage-Gated Na Channels
Christopher A. Beaudoin, Manas Kohli, Samantha C. Salvage, Hengrui Liu, Samuel J. Arundel, Samir W. Hamaia, Ming Lei, Christopher L.-H. Huang, Antony P. Jackson
In this study, Beaudoin et al. investigate the structural effects of N-linked glycosylation on NaV channels using molecular modeling and dynamics simulations. They show that isoform-specific glycosylation on NaV1.5 and NaV1.8 alters the binding sites of regulatory β-subunits, potentially contributing to β-subunit homo-oligomerization and NaV channel supramolecular clustering.
Issue Cover
Current Issue
Volume 157,
Issue 1,
6 January 2025
Reviews & Opinions
Commentary | Voltage-Gated Na Channels
Tanadet Pipatpolkai
Tao and Corry (2025) used metadynamics, an enhanced sampling method to identify and classify Nav channel blockers.
Review
Elizabeth Murphy, David A. Eisner
The regulation of mitochondrial calcium and its role in regulating cell death.
Research News
Ben Short
JGP study reveals that a sodium channel mutant blocks fast inactivation downstream of inactivation particle binding, diverting the channel into an alternative open state.

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