The Journal of Physiology publishes research in all areas of physiology and pathophysiology that illustrates new physiological principles, mechanisms or premises. Papers on work at the molecular level, cell membrane, single cells, tissues or organs, and on systems physiology are all encouraged. We are particularly keen on research that has a clinical or translational focus, to help further our understanding of the role physiology plays in health and disease.

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Unlocking the full potential of high‐density surface EMG: novel non‐invasive high‐yield motor unit decomposition

  •  17 March 2025

Graphical Abstract

Schematics of the HD-sEMG data used in the analysis Effect of excitation level on the number of motor units found and characteristics of the decomposed motor units Effect of method to prevent repeated convergence to the same source and exponent of the contrast function on the number of motor units found Effect of noise on the number of motor units found and the RoA with the ground truth for 30 %MVC force level Representative example of a unit in a ballistic contraction decomposed with 100% accuracy Effect of ballistic task on the number of motor units found and the RoA with the ground truth Effect of the decomposition algorithm used on experimental data Effect of the decomposition algorithm used on experimental data Effect of the decomposition algorithm used on experimental data recorded at the forearm of two female participants Unlocking the full potential of high-density surface EMG: novel non-invasive high-yield motor unit decomposition Issue ,

Abstract figure legend Schematic of Swarm-Contrastive Decomposition. A set of separation vectors are initialised to the same vector, with zero-mean and unitary standard deviation. Each separation vector is associated with a specific particle, the value of the exponent in the contrast function. This value tunes the sensitivity of the contrast function to outliers. Each separation vector is updated independently given a measure of sparsity of the produced source vector. The exponents are updated based on the optimal value with a particle swarm optimisation algorithm. The final outputs are the peaks of the source vector, which represent the firing times of the current motor unit. The process is repeated in an iterative fashion until all motor units are decomposed. Created in BioRender. Grison, A. (2025) https://BioRender.com/y04h318

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Interictal discharges spread along local recurrent networks between tubers and surrounding cortex

  •  17 March 2025

Graphical Abstract

Dynamic causal modelling Selection of representative interictal discharges for dynamic causal modelling Delays follow a tuber core to periphery gradient Recurrent coupling in local networks supports IED Only networks with recurrent coupling support IED- and seizure-like dynamics Interictal discharges spread along local recurrent networks between tubers and surrounding cortex Issue ,

Abstract figure legendInterictal epileptiform discharges (IEDs) indicate irritable cortex and may arise from brain lesions such as cortical tubers in tuberous sclerosis. Here, we identify IEDs in intracranial recordings in patients undergoing evaluation for epilepsy surgery, and demonstrate that they behave like a travelling wave arising from the tuber core. Using a neural mass model, we then demonstrate that recurrently coupled networks allow for the fast spread of IEDs along the tuber and perituberal cortical areas (left). Simulating a reduction of inhibitory connectivity, the fully parameterised network model then indicates that these recurrent networks, but not other types of network architectures, are capable of generating interictal epileptiform discharges, as well as seizure-like dynamics (right)

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Neuromuscular junction instability with inactivity: morphological and functional changes after 10 days of bed rest in older adults

  •  17 March 2025

Graphical Abstract

Representative images of endplate occupancy assessed by colocalisation staining of presynaptic (synaptic vesicle protein 2; SV2) and postsynaptic (acetylcholine receptor; AChR) terminals Comparison of bed rest effects on the neuromuscular junction (NMJ) terminals overlap and C-terminal agrin fragment (CAF) levels in older participants with and without interventions Alterations of the neuromuscular junction (NMJ) terminals overlap and NMJ occupancy Morphological alterations of the neuromuscular junction postsynaptic terminal (acetylcholine receptors; AChR) Circulating C-terminal agrin fragment (CAF) concentration before (BR0) and after 10 days (BR10) of bed rest Changes in motor unit potentials (MUP) recorded using intramuscular EMG Changes in near-fibre EMG parameters obtained using intramuscular EMG Neuromuscular junction instability with inactivity: morphological and functional changes after 10 days of bed rest in older adults Issue ,

Abstract figure legend This figure summarises the study of neuromuscular junction (NMJ) changes in 10 older males following a 10 day bed rest period. Baseline (BR0) and post-bed rest (BR10) assessments were conducted using intramuscular EMG (iEMG) to measure NMJ transmission. At BR0 and BR10, muscle biopsies were obtained to analyse NMJ morphology, and blood samples were collected to evaluate C-terminal agrin fragment (CAF) levels, a biomarker of NMJ instability and acetylcholine receptor (AChR) remodelling. After the bed rest period, NMJ morphology showed reduced overlap between presynaptic and postsynaptic terminals and an increase in AChR area. Elevated CAF levels biochemically confirmed this AChR remodelling. Additionally, NMJ transmission properties were impaired, suggesting that this NMJ morphological remodelling is associated with functional alterations.

Antiarrhythmic effects of mirabegron on ventricular fibrillation in Langendorff‐perfused rabbit ventricles

  •  14 March 2025

Graphical Abstract

Antiarrhythmic effects of mirabegron on ventricular fibrillation (VF) during isoproterenol (ISO) infusion Effects of mirabegron on conduction velocity during isoproterenol (ISO) infusion Effects of mirabegron on action potential duration (APD) during isoproterenol (ISO) infusion Time control experiment Dose-dependent antiarrhythmic effects of mirabegron without pretreatment with isoproterenol (ISO) Dose-dependent effects of mirabegron (Mira) on conduction velocity without pretreatment with isoproterenol (ISO) Absence of effect of mirabegron on heterologously expressed SK2 currents Antiarrhythmic effects of mirabegron on ventricular fibrillation in Langendorff-perfused rabbit ventricles Issue ,

Abstract figure legend Optical mapping studies in Langendorff perfused rabbit hearts showed that isoproterenol (ISO) significantly increased the number of phase singularities (PSs) per ventricular fibrillation episode in females and the dominant frequency (DF) in both sexes. Mirabegron, a β-3 adrenoceptor agonist, significantly decreased the PSs in both sexes and significantly decreased DF in females. It also reduced conduction velocity (CV) in females not in males. Without ISO, females showed significantly lower PSs than males at mirabegron concentrations of 750 nm and 1000 nm. RT-quantitative PCR analysis showed no sex difference in β-3 adrenoceptor RNA expression. Mirabegron did not inhibit IKAS in human embryonal kidney 293 cells. These findings suggest that mirabegron, a β-3 AR agonist, is antiarrhythmic, and its antiarrhythmic properties are more commonly observed in females than males.

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Issue Information

  •  1335-1336
  •  14 March 2025
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Biophysical modelling of intrinsic cardiac nervous system neuronal electrophysiology based on single‐cell transcriptomics

  •  12 March 2025

Graphical Abstract

Workflow for development of electrophysiological models starting with single neuron gene expression data and model database of ion channel kinetics Selection of expression threshold for filtering transcriptomic data Neuronal genotypes resulting from thresholded single neuron gene expression data on ion channels Comparison of activation and inactivation curves for alternative ion channel models Neuronal firing behaviour with increasing stimulus strength Effect of varying the Nav1.1 channel inactivation parameter (h∞) on electrophysiological behaviour Current–frequency relationship for tonically firing neurons Relative expression ratios correlate with maximal conductances identified in the model Biophysical modelling of intrinsic cardiac nervous system neuronal electrophysiology based on single-cell transcriptomics Issue ,

Abstract figure legend The intrinsic cardiac nervous system regulates the beat-to-beat function of the heart. Hodgkin–Huxley ion channel models from literature were selected based on the ion channels found in single-neuron transcriptomic data. The transcriptomic data were binarized to confer combinations of ion channel presence or absence for each neuron in a library of parallel conductance models. The model-predicted electrophysiological behaviour reflects the distribution of firing patterns observed experimentally. These models are a first step towards bridging the gap between single-cell transcriptomic data and predictive models of physiology.

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