Journal of General Physiology

Journal of General Physiology The Journal of General Physiology publishes research in physiological problems at cellular and molecular level. Published by Rockefeller University Press.

The Journal of General Physiology publishes peer-reviewed research in biological, chemical, or physical mechanisms of broad physiological significance, with an emphasis on physiological problems at the cellular and molecular level. Areas include, but are not limited to:

- Membrane protein physiology
- Protein structure and dynamics
- Lipid and membrane biophysics
- Cell mechanics
- Intracellular

and intercellular signaling

All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JGP provides free online access to many article types from the date of publication and to all archival content. Established in 1918, JGP is published by The Rockefeller University Press. For more information, visit http://jgp.rupress.org. Follow us on Twitter: https://twitter.com/JGenPhysiol

Christian Jorgensen (University of Portsmouth) discusses new study from Elhanafy et al. (https://hubs.la/Q033L5mt0) whi...
01/23/2025

Christian Jorgensen (University of Portsmouth) discusses new study from Elhanafy et al. (https://hubs.la/Q033L5mt0) which used Molecular Dynamics simulations and electrophysiology to show how identical mutations in the voltage sensing domain of sodium channels can yield differential functional effects. https://hubs.la/Q033L1Ys0

Phil Alexander Köster, Thomas Stiehl, Angelika Lampert and colleagues (Uniklinik RWTH Aachen) characterize eight sodium ...
01/21/2025

Phil Alexander Köster, Thomas Stiehl, Angelika Lampert and colleagues (Uniklinik RWTH Aachen) characterize eight sodium channel subtypes relevant to nociception and use a computer model to simulate the response of two types of nociceptive nerve fibers. Their results provide a better understanding of Nav1.7 and Nav1.9 and have implications for future mechanistic studies and disease modeling. https://hubs.la/Q033lb8Z0

Eslam Elhanafy, Jing Li et al. (University of Mississippi - Department of BioMolecular Sciences) show that identical mut...
01/17/2025

Eslam Elhanafy, Jing Li et al. (University of Mississippi - Department of BioMolecular Sciences) show that identical mutations at equivalent positions in VSDs of cardiac sodium channels can lead to diverse functional effects. Using molecular dynamics simulations, they uncover VSD-specific structural dynamics and gating-pore conformations that explain these differential impacts, advancing our understanding of sodium channelopathies. https://hubs.la/Q032-RfR0

Commenary from Tanadet Pipatpolkai (Nanyang Technological University, Singapore) on a new study by Tao and Corry (https:...
01/08/2025

Commenary from Tanadet Pipatpolkai (Nanyang Technological University, Singapore) on a new study by Tao and Corry (https://hubs.la/Q031sxNN0) that uses an enhanced sampling method, metadynamics, to identify and classify Naᵥ channel blockers. https://hubs.la/Q031sq6F0

Elaine Tao and Ben Corry (The Australian National University) investigate the binding of sodium channel inhibitors to th...
01/07/2025

Elaine Tao and Ben Corry (The Australian National University) investigate the binding of sodium channel inhibitors to the Nav1.5 pore using simulations, revealing 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. https://hubs.la/Q031smRx0

Our January issue is here! https://hubs.la/Q0314VBJ0The cover shows agonist-induced opening of human NMDA receptors, a p...
01/06/2025

Our January issue is here! https://hubs.la/Q0314VBJ0
The cover shows agonist-induced opening of human NMDA receptors, a prominent neurotransmitter-gated ion channel, assayed using single channel outside-out patches to detect varied activation delays (blue) and failures (red). GluN2B-containing receptors, compared to GluN2A-containing ones, activate inefficiently, highlighting their distinct activation mechanism.
At synapses, NMDA receptors convert presynaptically released glutamate into a synaptic signal. Miaomiao He and Lonnie Wollmuth define the impact of various environmental factors and GluN2 subunit composition on the efficiency of rapid glutamate-induced channel opening. https://hubs.la/Q0314wPQ0

Alessandra Picollo and Michael Pusch (CNR Consiglio Nazionale delle Ricerche) present ALLIN (Annotation of sequence aLig...
01/02/2025

Alessandra Picollo and Michael Pusch (CNR Consiglio Nazionale delle Ricerche) 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. https://hubs.la/Q03107jS0

Sabrina Apel, Matthew Gage and colleagues (UMass Lowell) demonstrate that the calcium-binding protein S100A1 binds the N...
01/02/2025

Sabrina Apel, Matthew Gage and colleagues (UMass Lowell) 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. https://hubs.la/Q03100jH0

Defective Ca²⁺ signaling in muscle cells is thought to play a role in Duchenne muscular dystrophy. Jonathan Schreiber, V...
12/24/2024

Defective Ca²⁺ signaling in muscle cells is thought to play a role in Duchenne muscular dystrophy. Jonathan Schreiber, Vincent Jacquemond and colleagues (Université Claude Bernard Lyon 1) report that voltage-activated SR Ca²⁺ release is moderately depressed in muscle fibers isolated from a rat model that reproduces the human disease well. https://hubs.la/Q030B29j0

Smriti Gupta, Douglas Bayliss and colleagues (UVA Pharmacology Department) show that Pannexin 1 (PANX1) channels can fun...
12/20/2024

Smriti Gupta, Douglas Bayliss and colleagues (UVA Pharmacology Department) 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. https://hubs.la/Q030lB1M0

New Review: Elizabeth Murphy (National Institutes of Health (NIH)) and David Eisner (The University of Manchester) discu...
12/19/2024

New Review: Elizabeth Murphy (National Institutes of Health (NIH)) and David Eisner (The University of Manchester) discuss the regulation of mitochondrial calcium and its role in regulating cell death. https://hubs.la/Q030c1Mx0

Our latest Research News: Liu and Bezanilla (https://hubs.la/Q02_Yc_10) reveal that a sodium channel mutant blocks fast ...
12/17/2024

Our latest Research News: Liu and Bezanilla (https://hubs.la/Q02_Yc_10) reveal that a sodium channel mutant blocks fast inactivation downstream of inactivation particle binding, diverting the channel into an alternative open state. https://hubs.la/Q02_YjNj0

In this study, Lisa McIlvried, John Del Rosario, Robert Gereau and colleagues (WashU Medicine) show that mechanisms of a...
12/17/2024

In this study, Lisa McIlvried, John Del Rosario, Robert Gereau and colleagues (WashU Medicine) 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. https://hubs.la/Q02_Y1p40

Christopher Beaudoin, Antony Jackson and colleagues (Department of Biochemistry, University of Cambridge) investigate th...
12/16/2024

Christopher Beaudoin, Antony Jackson and colleagues (Department of Biochemistry, University of Cambridge) 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. https://hubs.la/Q02_NDqw0

Commentary from Joan Chan and Michelle Munro (University of Otago): Hanna et al. (https://hubs.la/Q02_rgxq0) reveal that...
12/12/2024

Commentary from Joan Chan and Michelle Munro (University of Otago): Hanna et al. (https://hubs.la/Q02_rgxq0) reveal that early, but not late, developmental cardiac FKBP12 deficiency leads to dilated cardiomyopathy in the adult heart. https://hubs.la/Q02_r8dL0

Amy Hanna, Ting Chang, Kevin Ho, Susan Hamilton and colleagues Baylor College of Medicine generate two conditional mouse...
12/11/2024

Amy Hanna, Ting Chang, Kevin Ho, Susan Hamilton and colleagues Baylor College of Medicine generate two conditional mouse models of embryonic loss of FKBP12 in cardiomyocytes. Their findings show a progressive development of dilated cardiomyopathy, cardiac oxidative stress, and calcium leak, and suggest a role for FKBP12 in embryonic cardiac muscle. https://hubs.la/Q02_gwBk0

Our December issue is here! https://hubs.la/Q02ZCLsQ0The cover features the structural model of TRAP transporter VcGluPQ...
12/02/2024

Our December issue is here! https://hubs.la/Q02ZCLsQ0
The cover features the structural model of TRAP transporter VcGluPQM, showing the substrate binding protein (red) interacting with the scaffold (blue), transport (orange), and claw (purple) domains of the membrane component.

Work from Joseph Davies, Christopher Mulligan and colleagues on the structure and selectivity of a TAXI TRAP transporter binding protein reveals new ligand binding details and a previously unreported membrane component architecture (https://hubs.la/Q02ZCL720).

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Pengfei Liang, Huanghe Yang (Duke University School of Medicine) and colleagues reveal that niclosamide, a proposed TMEM16A inhibitor for asthma and COPD, unexpectedly enhances TMEM16A activity, raising caution for its
Pengfei Liang, Huanghe Yang (Duke University School of Medicine) and colleagues reveal that niclosamide, a proposed TMEM16A inhibitor for asthma and COPD, unexpectedly enhances TMEM16A activity, raising caution for its

Pengfei Liang, Huanghe Yang (Duke University School of Medicine) and colleagues reveal that niclosamide, a proposed TMEM16A inhibitor for asthma and COPD, unexpectedly enhances TMEM16A activity, raising caution for its clinical use. They also discover its binding site on TMEM16A, aiding in developing targeted modulators for various diseases. https://hubs.la/Q02yZGmj0

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Today on #InternationalWomensDay we celebrate women scientists #WomenInSTEM who continue to #BreakTheBias! Happy #IWD2022 #WHM2022 https://www.internationalwomensday.com

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We're Hiring a Scientific Managing Editor
We're Hiring a Scientific Managing Editor

The Journal of General Physiology (JGP) and Journal of Experimental Medicine (JEM) seek a talented individual for the role of Scientific Managing Editor. Learn more and apply: https://bit.ly/34djCGX

K+ moving through the GIRK2 (Kir3.2) ion channel pore
K+ moving through the GIRK2 (Kir3.2) ion channel pore

K+ movement through the two subunits of the GIRK2 (Kir3.2) ion channel (side view). The permeating K+ ion is colored in dark purple, and other K+ ions are colored in pink. Water inside the channel pore is shown. Video from Bernsteiner et al. 2019 in JGP https://bit.ly/2Q9zCqI

Compression of the NOMPC helical bundle
Compression of the NOMPC helical bundle

Our senses of touch and hearing are dependent on the conversion of external mechanical forces into electrical impulses by the opening of mechanosensitive channels in sensory cells. The mechanosensitive channel NOMPC is responsible for hearing and touch in flies. This video indicates how the NOMPC chains deform and the gating region moves in a model generated by Argudo et al. 2019 in JGP https://bit.ly/2Wqw4ib #physiology

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