Muscle Fiber Action Potentials Research Articles

A-019 Integrative Analysis of Arrythmogenic Right Ventricular Cardiomyopathy of Potencial Biomarkers Through Bioinformatic Analysis

Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease usually associated with heterozygous or compound mutations in cardiac desmosomes genes. Pathologically, it is a disease characterized by fibrofatty replacement primarily in the right ventricle of normal cardiac tissue and clinically by sudden cardiac death in healthy young people. Diagnosis is often difficult due to the nonspecific nature of the disease and the broad spectrum of phenotypic variations, being commonly diagnostic post mostem. Non-coding RNAs are biomarkers that regulate gene expression and participate in various pathophysiological processes, becoming an important research field in cardiomyopathology for their potential as non-invasive clinical biomarkers and therapeutic. In this study, we aim to identify miRNAs that may serve as potentially effective targets in diagnosis and treatment as well as the exploration of regulatory miRNAs-mRNAs networks is beneficial for comprehensively understanding the molecular mechanism of ARVC development. Methods This study screened RNAs expression profiling studies from the Gene Expression Omnibus (GEO) database. The keyword “arrhythmogenic right ventricular cardiomyopathy” was used to search for suitable datasets that followed the criteria of being a comparable case-control human study, it was selected the GSE29819 and GSE164490 GEO series. The microarray GSE29819 set was analyzed using GEO2R, an interactive web tool disponibility in GEODataset site, resulting in the differential expression genes (DEGs) of this series, while high throughput sequencing GSE164490 set was preprocessing by miARma-Seq v 1.7.5 and for identifying DEGs was used R software v4.2.2 in R Studio (version: 2022.12.0 + 353) and Deseq2 package. The 2 sets used P < 0.05 and |log FC| > 1.5 as the cutoff criteria. An online prediction database, DIANA-microT CDS v 5.0 was used to obtain interactions with high confidence levels between miRNAs and target mRNAs. STRING online database v9 was used to predict protein-protein interactions (PPI) and functional enrichment analysis was conducted using the web-based utility Enrichr to uncover the roles of these molecules. Results The integrated analysis of the 2 datasets from GEO sequencing data from ARVC, after a criterium analysis, identify 04 common DEGs: hsa-miR-30d-5p, hsa-miR-200a-3p, hsa-miR-34a-5p and hsa-miR-125a-5p between them. Also, by constructing a PPI network, it was identified 04 genes among the overlapping DEGs, including PIK3R2, RARRES1, SCN2B, and SLCO5A1 (scores ≥0.7). The functional enrichment analyses demonstrated that the DEGs were enriched in some GO biological processes such as regulation of atrial cardiac muscle cell membrane and voltage-gated sodium channel activity involved in cardiac muscle cell action potential. Conclusion Our results suggest that these new network gene associations possibly play a potential role in metabolic pathways related to the pathogenesis of ARVC and are good candidates for further functional validation assays to confirm these findings.

Neuromuscular junction transmission failure in aging and sarcopenia: The nexus of the neurological and muscular systems.

Sarcopenia, or age-related decline in muscle form and function, exerts high personal, societal, and economic burdens when untreated. Integrity and function of the neuromuscular junction (NMJ), as the nexus between the nervous and muscular systems, is critical for input and dependable neural control of muscle force generation. As such, the NMJ has long been a site of keen interest in the context of skeletal muscle function deficits during aging and in the context of sarcopenia. Historically, changes of NMJ morphology during aging have been investigated extensively but primarily in aged rodent models. Aged rodents have consistently shown features of NMJ endplate fragmentation and denervation. Yet, the presence of NMJ changes in older humans remains controversial, and conflicting findings have been reported. This review article describes the physiological processes involved in NMJ transmission, discusses the evidence that supports NMJ transmission failure as a possible contributor to sarcopenia, and speculates on the potential of targeting these defects for therapeutic development. The technical approaches that are available for assessment of NMJ transmission, whether each approach has been applied in the context of aging and sarcopenia, and the associated findings are summarized. Like morphological studies, age-related NMJ transmission deficits have primarily been studied in rodents. In preclinical studies, isolated synaptic electrophysiology recordings of endplate currentsor potentials have been mostly used, and paradoxically, have shown enhancement, rather than failure, with aging. Yet, in vivo assessment of single muscle fiber action potential generation using single fiber electromyography and nerve-stimulated muscle force measurements show evidence of NMJ failure in aged mice and rats. Together these findings suggest that endplate response enhancement may be a compensatory response to post-synaptic mechanisms of NMJ transmission failure in aged rodents. Possible, but underexplored, mechanisms of this failure are discussed including the simplification of post-synaptic folding and altered voltage-gated sodium channel clustering or function. In humans, there is limited clinical data that has selectively investigated single synaptic function in the context of aging. If sarcopenic older adults turn out to exhibit notable impairments in NMJ transmission (this has yet to be examined but based on available evidence appears to be plausible) then these NMJ transmission defects present a well-defined biological mechanism and offer a well-defined pathway for clinical implementation. Investigation of small molecules that are currently available clinically or being testing clinically in other disorders may provide a rapid route for development of interventions for older adults impacted by sarcopenia.

Muscle fiber conduction velocity in situ revisited: A new approach to an ancient technique.

The aim of this study was to measure the muscle fiber conduction velocity (MFCV) in situ in the tibialis anterior muscle in healthy subjects. A total of 36 subjects matched for age and sex were studied. The MFCV was measured with a concentric needle by intramuscular monopolar needle electrical activation at a distance of 50 mm. The mean consecutive difference (MCD) of <5 μs was obtained after a median of 62 muscle fiber action potentials (MFAPs), confirming a direct muscle fiber activation. The measuring latency was at the median point of ascending depolarizing line of the MFAP. The calculated MFCV from 784 MFAPs was 4.10 ± 0.66 m/s, 3.99 ± 0.57 for female subjects (95%, 2.85 to 5.13), and 4.20 ± 0.73 for male subjects (95%, 2.74 to 5.67). The MFCV was 5.22% faster in male subjects. The calculated fast-to-slow MFCV ratio (F/S ratio) was 1.47 for female subjects (95%, 1.27 to 2.54) and 1.67 for male subjects (95%, 1.31 to 3.74). Aging significantly increased the F/S ratio. As the MFCVs mainly depend on the muscle diameter, their assessment is a quick and helpful tool for estimating it. Its variability by the F/S ratio is also a powerful tool in the follow-up of some neuromuscular disorders.

Gating defects in K1126I, a putative hypokalemic periodic paralysis mutation in hNav1.4.

We investigated the impact of mutation K1126I reported to be associated with hypokalemic periodic paralysis, but not yet characterized. The location of this mutation is the extracellular positive charge in domain III S4, and characterization of artificial mutations at this locus suggest it is outside the electric field. We used cut-open oocyte electrophysiology to characterize the steady-state and kinetic gating parameters in wild type hNaV1.4, K1126I in both the native background and with incorporation of the 1303IFM/QQQ mutation to isolate activation from fast inactivation. K1126I produced an 11 mV hyperpolarizing (left-)shift in the midpoint of the steady-state fast inactivation curve, and decreased slope. Activation midpoint was left-shifted by 4 mV by K1126I with decreased slope. Recovery from fast inactivation was slowed and entry from closed states was accelerated by K1126I, with open-state fast inactivation and deactivation not significantly altered. Simulated action potentials for which steady-state fast inactivation and activation parameters were incorporated showed a 10 mV attenuation of the skeletal muscle fiber action potential. We used the IFM/QQQ background to compare slow inactivation in wild type and K1126I channels. The midpoint of the steady-state slow inactivation was hyperpolarized by 8 mV in K1126I/QQQ compared to hNaV1.4 / QQQ, with onset unaffected and recovery accelerated. This work was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant #P20GM103408.

Marginal zinc deficiency alters the heart proteome of rats.

Zinc deficiency is closely related to cardiovascular diseases (CVDs), but the effects of marginal zinc deficiency (MZD) after birth on the heart are unknown. In this study, 4-week-old male rats were fed a low zinc diet (10 mg kg-1, 1/3 recommended nutrient intake, RNI) for 8 weeks. Echocardiography and histopathology were performed to assess the functional and morphological alterations of the heart. High-throughput proteomics was used to study the effects of MZD on cardiac protein expression. We found that MZD reduced food intake, body weight, serum zinc, and heart weight; however, the coefficient, zinc concentration, function, and histopathology of the heart were not changed. The heart proteome was altered in the marginal zinc-deficient diet group (MZG), compared with the normal zinc diet group (NZG). A total of 310 differentially expressed proteins (P < 0.05) were significantly changed by MZD, among which 163 proteins were up-regulated and 147 were down-regulated. Of these, 43 proteins are related to CVDs and 18 proteins are zinc-associated proteins. Gene Ontology and Pathway analysis revealed that 74 biological processes (BPs) and 37 pathways were significantly changed by MZD. This included six CVD-related BPs, such as regulation of heart rate, cardiac muscle contraction, regulation of ventricular cardiac muscle cell action potential, and regulation of blood pressure, and eight CVD-related pathways, such as dilated cardiomyopathy, diabetic cardiomyopathy, and hypertrophic cardiomyopathy. Our data show that marginal zinc deficiency after birth significantly alters cardiac protein expression and pathways related to CVDs.

Teaching Essential EMG Theory to Kinesiologists and Physical Therapists Using Analogies Visual Descriptions, and Qualitative Analysis of Biophysical Concepts.

Electromyography (EMG) is a multidisciplinary field that brings together allied health (kinesiology and physical therapy) and the engineering sciences (biomedical and electrical). Since the physical sciences are used in the measurement of a biological process, the presentation of the theoretical foundations of EMG is most conveniently conducted using math and physics. However, given the multidisciplinary nature of EMG, a course will most likely include students from diverse backgrounds, with varying levels of math and physics. This is a pedagogical paper that outlines an approach for teaching foundational concepts in EMG to kinesiologists and physical therapists that uses a combination of analogies, visual descriptions, and qualitative analysis of biophysical concepts to develop an intuitive understanding for those who are new to surface EMG. The approach focuses on muscle fiber action potentials (MFAPs), motor unit action potentials (MUAPs), and compound muscle action potentials (CMAPs) because changes in these waveforms are much easier to identify and describe in comparison to the surface EMG interference pattern (IP).

Consensus for experimental design in electromyography (CEDE) project: High-density surface electromyography matrix

High-density surface electromyography (HDsEMG) can be used to measure the spatial distribution of electrical muscle activity over the skin. As this distribution is associated with the generation and propagation of muscle fiber action potentials, HDsEMG is processed to extract information on regional muscle activation, muscle fiber characteristics and behaviour of individual motor units. This matrix, developed by the Consensus for Experimental Design in Electromyography (CEDE) project, summarizes recommendations on the use of HDsEMG in experimental studies. For each application, recommendations are included regarding electrode montage, electrode type and configuration, electrode location and orientation, data analysis, and interpretation. Cautions and reporting standards are also included. The steps of the Delphi process to reach consensus are contained in an appendix. This matrix is intended to help researchers when collecting, reporting, and interpreting HDsEMG data. It is hoped that this document will be used to generate new empirical evidence to improve how HDsEMG is used in research and in clinical applications.

Electromyography of the muscle spindle

In needle electromyography, there are two spontaneous waveforms, miniature end plate potentials and “end plate spikes”, appearing usually together. Miniature end plate potentials are local, non-propagating postsynaptic waves, caused by spontaneous exocytosis of acetylcholine in the neuromuscular junction. The prevailing hypothesis states that “end plate spikes” are propagated postsynaptic action potentials of muscle fibers, caused by presynaptic irritation of the motor nerve or nerve terminal. Using several small concentric needle electrodes in parallel with the muscle fibers, most “end plate spikes” are strictly local or propagating for 2–4 mm. At the end plate zone, there are miniature end plate potentials without “end plate spikes”. Local “end plate spikes” are junctional potentials of intrafusal gamma neuromuscular junctions of the nuclear bag fibers, and propagated “end plate spikes” are potentials of nuclear chain muscle fibers of muscle spindles. Miniature end plate potentials without “end plate spikes” at the end plate zone derive from alpha neuromuscular junctions. These findings contrast with the prevailing hypothesis. The history of observations and different hypotheses of the origin of end plate spikes are described.

Electrical cross-sectional imaging of human motor units in vivo

ObjectivesIn many neuromuscular diseases, weakness results from a disruption in muscle fibres' arrangement within a motor unit. Limitations in current techniques mean that the spatial distribution of fibres in human motor units remains unknown. MethodsA flexible multi-channel electrode was developed and bonded to a clinical electromyography (EMG) needle. Muscle fibre action potentials were localised using a novel deconvolution method. This was tested using simulated data, and in recordings collected from the tibialis anterior muscle of healthy subjects. ResultsSimulated data indicated good localisation reliability across all sections of the electrode except the end sections. A corrected fibre density was estimated up to 1.4 fibres/mm2. Across five recordings from three individuals, between 4 and 14 motor units were detected. Between 1 and 20 muscle fibres were localised per motor unit within the electrode detection area, with up to 220 muscle fibres localised per recording, with overlapping motor unit territories. ConclusionsWe provide the first direct evidence that human motor units spatially overlap, as well as data related to the spatial arrangement of muscle fibres within a motor unit. SignificanceAs well as providing insights into normal human motor physiology, this technology could lead to faster and more accurate diagnosis in patients with neuromuscular diseases.

Marching band model for simulating a single muscle fiber action potential

ObjectiveWe describe a mathematical model to calculate a single muscle fiber action potential (AP). Based on a marching band pattern, it is an enhancement to our previously described “modified line source” model. MethodsCalculations were performed using an Excel spread sheet. AP was simulated for a 200 mm long muscle fiber with 60 µm diameter, propagation velocity of 4 m/s, and end-plate located at the center. Several different electrode locations were used to calculate the AP. ResultsThe AP amplitude was highest at the end-plate where the waveform was biphasic with initial negativity. When the electrode was moved towards the tendon, the amplitude decreased for the first 1.5 mm. The AP was triphasic and its waveform was relatively constant at electrode positions beyond 1.5 mm from the end-plate. It matched the calculations using the modified line source model. When the electrode was near the tendon, the AP amplitude decreased asymmetrically and waveform became biphasic resembling a positive sharp wave. DiscussionThe model is conceptually and computationally simple. It simulated the expected AP shape at different electrode positions along the muscle fiber. The waveforms are similar to those obtained from mathematically complex volume conductor models. SignificanceThe revised model can be useful for teaching and future simulation studies.

WS6.2. Stimulation single-fibre EMG: Methods and pitfalls (with demonstration)

Single-fiber electromyography (SFEMG) is a technique introduced by Prof. Stålberg and his colleagues in 1970’s. SFEMG electrode has the smallest uptake area (0.3 mm in radius) among EMG electrodes, and therefore can identify action potentials of individual muscle fibers (single fiber action potentials; SFAPs) comprising the motor unit by applying a very high low- cut filter (500 Hz). Recently, disposable concentric needle is commonly used in place of reusable SFEMG needle (CN-SFEMG). By setting an even higher low-cut filter (1 or 2 kHz), individual SFAPs can be identified even using the concentric needle. There are two recording methods of SFEMG, during voluntary contraction (v-SFEMG) and following axonal stimulation (s-SFEMG). Both methods have merits and demerits, and specific pitfalls. Patient cooperation is necessary for v-SFEMG but not for s-SFEMG, which is therefore applicable for comatose patients or small children. Examination time is usually believed to be shorter in s-SFEMG (I don’t think that this is always true). This is because only one SFAP is necessary in order to measure jitter in s-SFEMG, although two SFAPs recoded simultaneously are necessary in v-SFEMG. However, v-SFEMG is probably more sensitive in detecting neuromuscular junction (NMJ) dysfunction in myasthenia gravis (MG). Since SFEMG is expected to be more sensitive than repetitive nerve stimulation test, the sensitivity must be the most crucial issue. Therefore, I prefer v-SFEMG and conduct only v-SFEMG in daily practice. For s-SFEMG, monopolar stimulating needle is inserted close to the motor nerve or terminal nerve twigs (facial nerve branch lateral to the external canthus for frontalis recording). CN needle is inserted within the target muscle. We search sharp SFAPs during 5 to10 Hz test stimulation. When good SFAPs are identified, jitter is measured during 10 Hz stimulation. Submaximal stimulation is the greatest pitfall in s-SFEMG. Therefore, the threshold current is determined for each SFAP and an intensity 20% over the threshold is used for recording jitter. Very often, the target SFAP is blurred by the contamination of other SFAPs that have been newly-recruited while increasing the current intensity. This Is the reason why s-SFEMG takes longer time than usually considered.

High-Resolution Structures of K+ Channels.

Potassium channels are present in every living cell and essential to setting up a stable, non-zero transmembrane electrostatic potential which manifests the off-equilibrium livelihood of the cell. They are involved in other cellular activities and regulation, such as the controlled release of hormones, the activation of T-cells for immune response, the firing of action potential in muscle cells and neurons, etc. Pharmacological reagents targeting potassium channels are important for treating various human diseases linked to dysfunction of the channels. High-resolution structures of these channels are very useful tools for delineating the detailed chemical basis underlying channel functions and for structure-based design and optimization of their pharmacological and pharmaceutical agents. Structural studies of potassium channels have revolutionized biophysical understandings of key concepts in the field - ion selectivity, conduction, channel gating, and modulation, making them multi-modality targets of pharmacological regulation. In this chapter, I will select a few high-resolution structures to illustrate key structural insights, proposed allostery behind channel functions, disagreements still open to debate, and channel-lipid interactions and co-evolution. The known structural consensus allows the inference of conserved molecular mechanisms shared among subfamilies of K+ channels and makes it possible to develop channel-specific pharmaceutical agents.

Wrestle while you learn: EMG as a teaching tool for undergraduate skeletal muscle physiology teaching.

Wrestle while you learn: EMG as a teaching tool for undergraduate skeletal muscle physiology teaching.

Site-dependent thenar compound muscle action potential: Comparison between surface and needle recordings

Within the thenar eminence, the median nerve innervates three muscles: abductor pollicis brevis (APB), flexor pollicis brevis (FPB), and opponens pollicis (OP). Of these muscles, APB was often considered as the sole contributor to the thenar compound muscle action potential (CMAP). To evaluate subcomponents of the thenar CMAP from the median nerve innervated muscles. Surface and needle CMAPs were recorded in normal human subjects from three recording sites: proximal (site-I), middle (site-II), and distal (site-III) aspects of the thenar eminence when the median nerve was activated at the wrist. In the site-I and -II, both the surface and needle CMAPs shared many similar characteristics although the needle CMAPs were larger (∼ 5 folds) and briefer (∼ 60%, needle/surface duration). In addition, on the surface recording, the CMAP was larger (by ∼ 1.9 mV) when recorded from the site-I comparing to that of the site-II. In the site-III, the surface recordings registered a delayed (by ∼ 3.8 ms) CMAP. The muscle fiber action potential (MFAP) study suggested a predominant FPB contribution in the site-III. The optimal recording site for APB derived thenar CMAP is the site-I and for FPB is the site-III. The CMAPs registered by the needle recordings are more robust than the surface ones.

β-Catenin Controls the Electrophysiologic Properties of Skeletal Muscle Cells by Regulating the α2 Isoform of Na+/K+-ATPase.

β-Catenin is a key component of the canonical Wnt signaling pathway. It has been shown to have an important role in formation of the neuromuscular junction. Our previous studies showed that in the absence of β-catenin, the resting membrane potential (RMP) is depolarized in muscle cells and expression of the α2 subunit of sodium/potassium adenosine triphosphatase (α2NKA) is reduced. To understand the underlying mechanisms, we investigated the electrophysiologic properties of a primary cell line derived from mouse myoblasts (C2C12 cells) that were transfected with small-interfering RNAs and over-expressed plasmids targeting β-catenin. We found that the RMP was depolarized in β-catenin knocked-down C2C12 cells and was unchanged in β-catenin over-expressed muscle cells. An action potential (AP) was not released by knockdown or over-expression of β-catenin. α2NKA expression was reduced by β-catenin knockdown, and increased by β-catenin over-expression. We showed that β-catenin could interact physically with α2NKA (but not with α1NKA) in muscle cells. NKA activity and α2NKA content in the cell membranes of skeletal muscle cells were modulated positively by β-catenin. These results suggested that β-catenin (at least in part) regulates the RMP and AP in muscle cells, and does so by regulating α2NKA.

Spectro-temporal analysis of electromyogram signals

Electromyography (EMG) signals can be used for clinical/biomedical applications, that measures electrical currents generated in muscles during its contraction representing neuromuscular. Individual muscle fibre action potentials are sometimes acquired using wire or needle electrodes placed directly in the muscle (invasive) or by a surface electrode (non-invasive). The combination of the muscle fibre action potentials from all the muscle fibres of a single motor unit is the motor unit action potential (MUAP). The simple detection with electrodes is insufficient to diagnose some neuromuscular diseases. The efficiency of diagnosis can be improved considerably by using modern signal processing techniques. The aim of this study is to analyse EMGs signals using temporal and frequency analysis. This analysis can provide a wide range of information's related to the type of signal (normal and pathological).

Rapid deformation of IPMC under a high electrical pulse stimulus inspired by action potential

Slow deformation seriously restrains application development of IPMC actuator, especially for thick and ionic liquid-based IPMC. Inspired by the action potential of muscle cell, this letter proposes a concept of high electrical pulse stimulus to accelerate IPMC deformation. By analyzing the dynamic process of voltage drop at the electrode-polymer interface, high voltage pulse is proved theoretically to be safe for IPMC in a short time. After charging the electrical double layer at the interface, the voltage pulse should be reduced to a safe level before electrochemical reactions. In our experiments, applying various high voltage pulses to a thick IPMC, the deformation can be sped up a few hundred times at most without any electrolysis damage. The results strongly support the practicability of the impulsive driving method.

Identification of Key Pathways and Genes in Anaplastic Thyroid Carcinoma via Integrated Bioinformatics Analysis.

BackgroundTo provide a better understanding of anaplastic thyroid carcinoma (ATC) at the molecular level, this study aimed to identify the genes and key pathways associated with ATC by using integrated bioinformatics analysis.Material/MethodsBased on the microarray data GSE9115, GSE65144, and GSE53072 derived from the Gene Expression Omnibus, the differentially expressed genes (DEGs) between ATC samples and normal controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein–protein interaction (PPI) network was constructed and visualized, with which the hub gene nodes were screened out. Finally, modules analysis for the PPI network was performed to further investigate the potential relationships between DEGs and ATC.ResultsA total of 537 common DEGs were screened out from all 3 datasets, among which 247 genes were upregulated and 275 genes were downregulated. GO analysis indicated that upregulated DEGs were mainly involved in cell division and mitotic nuclear division and the downregulated DEGs were significantly enriched in ventricular cardiac muscle cell action potential. KEGG pathway analysis showed that the upregulated DEGs were mainly enriched in cell cycle and ECM-receptor interaction and the downregulated DEGs were mainly enriched in thyroid hormone synthesis, insulin resistance, and pathways in cancer. The top 10 hub genes in the constructed PPI network were CDK1, CCNB1, TOP2A, AURKB, CCNA2, BUB1, AURKA, CDC20, MAD2L1, and BUB1B. The modules analysis showed that genes in the top 2 significant modules of PPI network were mainly associated with mitotic cell cycle and positive regulation of mitosis, respectively.ConclusionsWe identified a series of key genes along with the pathways that were most closely related with ATC initiation and progression. Our results provide a more detailed molecular mechanism for the development of ATC, shedding light on the potential biomarkers and therapeutic targets.

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.

A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects.

Chloride Channels Take Center Stage in Acute Regulation of Excitability in Skeletal Muscle: Implications for Fatigue.

Initiation and propagation of action potentials in muscle fibers is a key element in the transmission of activating motor input from the central nervous system to their contractile apparatus, and maintenance of excitability is therefore paramount for their endurance during work. Here, we review current knowledge about the acute regulation of ClC-1 channels in active muscles and its importance for muscle excitability, function, and fatigue.