Action Potential Propagation Velocity Research Articles

Vast Parameter Space Exploration of the Virtual Brain: A Modular Framework for Accelerating the Multi-Scale Simulation of Human Brain Dynamics

Global neural dynamics emerge from multi-scale brain structures, with nodes dynamically communicating to form transient ensembles that may represent neural information. Neural activity can be measured empirically at scales spanning proteins and subcellular domains to neuronal assemblies or whole-brain networks connected through tracts, but it has remained challenging to bridge knowledge between empirically tractable scales. Multi-scale models of brain function have begun to directly link the emergence of global brain dynamics in conscious and unconscious brain states with microscopic changes at the level of cells. In particular, adaptive exponential integrate-and-fire (AdEx) mean-field models representing statistical properties of local populations of neurons have been connected following human tractography data to represent multi-scale neural phenomena in simulations using The Virtual Brain (TVB). While mean-field models can be run on personal computers for short simulations, or in parallel on high-performance computing (HPC) architectures for longer simulations and parameter scans, the computational burden remains red heavy and vast areas of the parameter space remain unexplored. In this work, we report that our HPC framework, a modular set of methods used here to implement the TVB-AdEx model for the graphics processing unit (GPU) and analyze emergent dynamics, notably accelerates simulations and substantially reduces computational resource requirements. The framework preserves the stability and robustness of the TVB-AdEx model, thus facilitating a finer-resolution exploration of vast parameter spaces as well as longer simulations that were previously near impossible to perform. Comparing our GPU implementations of the TVB-AdEx framework with previous implementations using central processing units (CPUs), we first show correspondence of the resulting simulated time-series data from GPU and CPU instantiations. Next, the similarity of parameter combinations, giving rise to patterns of functional connectivity, between brain regions is demonstrated. By varying global coupling together with spike-frequency adaptation, we next replicate previous results indicating inter-dependence of these parameters in inducing transitions between dynamics associated with conscious and unconscious brain states. Upon further exploring parameter space, we report a nonlinear interplay between the spike-frequency adaptation and subthreshold adaptation, as well as previously unappreciated interactions between the global coupling, adaptation, and propagation velocity of action potentials along the human connectome. Given that simulation and analysis toolkits are made public as open-source packages, this framework serves as a template onto which other models can be easily scripted. Further, personalized data-sets can be used for for the creation of red virtual brain twins toward facilitating more precise approaches to the study of epilepsy, sleep, anesthesia, and disorders of consciousness. These results thus represent potentially impactful, publicly available methods for simulating and analyzing human brain states.

Non-invasive estimation of muscle fibre size from high-density electromyography.

Because of the biophysical relation between muscle fibre diameter and the propagation velocity of action potentials along the muscle fibres, motor unit conduction velocity could be a non-invasive index of muscle fibre size in humans. However, the relation between motor unit conduction velocity and fibre size has been only assessed indirectly in animal models and in human patients with invasive intramuscular EMG recordings, or it has been mathematically derived from computer simulations. By combining advanced non-invasive techniques to record motor unit activity in vivo, i.e. high-density surface EMG, with the gold standard technique for muscle tissue sampling, i.e. muscle biopsy, here we investigated the relation between the conduction velocity of populations of motor units identified from the biceps brachii muscle, and muscle fibre diameter. We demonstrate the possibility of predicting muscle fibre diameter (R2 =0.66) and cross-sectional area (R2 =0.65) from conduction velocity estimates with low systematic bias (∼2% and ∼4% respectively) and a relatively low margin of individual error (∼8% and ∼16%, respectively). The proposed neuromuscular interface opens new perspectives in the use of high-density EMG as a non-invasive tool to estimate muscle fibre size without the need of surgical biopsy sampling. The non-invasive nature of high-density surface EMG for the assessment of muscle fibre size may be useful in studies monitoring child development, ageing, space and exercise physiology, although the applicability and validity of the proposed methodology need to be more directly assessed in these specific populations by future studies. KEY POINTS: Because of the biophysical relation between muscle fibre size and the propagation velocity of action potentials along the sarcolemma, motor unit conduction velocity could represent a potential non-invasive candidate for estimating muscle fibre size in vivo. This relation has been previously assessed in animal models and humans with invasive techniques, or it has been mathematically derived from simulations. By combining high-density surface EMG with muscle biopsy, here we explored the relation between the conduction velocity of populations of motor units and muscle fibre size in healthy individuals. Our results confirmed that motor unit conduction velocity can be considered as a novel biomarker of fibre size, which can be adopted to predict muscle fibre diameter and cross-sectional area with low systematic bias and margin of individual error. The proposed neuromuscular interface opens new perspectives in the use of high-density EMG as a non-invasive tool to estimate muscle fibre size without the need of surgical biopsy sampling.

Measuring Action Potential Propagation Velocity in Murine Cortical Axons

Measuring Action Potential Propagation Velocity in Murine Cortical Axons

Analysing vagus nerve spontaneous activity using finite element modelling

Objective. Finite element modelling has been widely used to understand the effect of stimulation on the nerve fibres. Yet the literature on analysis of spontaneous nerve activity is much scarcer. In this study, we introduce a method based on a finite element model, to analyse spontaneous nerve activity with a typical bipolar electrode recording setup, enabling the identification of spontaneously active fibres. We applied our method to the vagus nerve, which plays a key role in refractory epilepsy. Approach. We developed a 3D model including dynamic action potential (AP) propagation, based on the vagus nerve geometry. The impact of key recording parameters—inter-electrode distance and temperature—and uncontrolled parameters—fibre size and position in the nerve—on the ability to discriminate active fibres were quantified. A specific algorithm was implemented to detect and classify APs from recordings, and tested on six rat in-vivo vagus nerve recordings. Main results. Fibre diameters can be discriminated if they are below 3 μm and 7 μm, respectively for inter-electrode distances of 2 mm and 4 mm. The impact of the position of the fibre inside the nerve on fibre diameter discrimination is limited. The range of active fibres identified by modelling in the vagus nerve of rats is in agreement with ranges found at histology. Significance. The nerve fibre diameter, directly proportional to the AP propagation velocity, is related to a specific physiological function. Estimating the source fibre diameter is thus essential to interpret neural recordings. Among many possible applications, the present method was developed in the context of a project to improve vagus nerve stimulation therapy for epilepsy.

Using Plant Cells of Nitellopsis obtusa for Biophysical Education

ABSTRACT Using giant characeaen algae Nitellopsis obtusa in laboratory exercises is proposed to familiarize students with basic concepts of electrophysiology and provide some simple hands-on practice. The described concept experiments present extracellular registration of action potentials (APs) and investigation of cytoplasmic streaming properties. Students are expected to register the propagation velocity of APs (found to be 3.4 ± 1.5 cm/s in N. obtusa), as well as the velocity of cytoplasmic streaming (66.7 ± 9 μm/s). Proposed exercises also concern recovery dynamics of cytoplasmic streaming after a stimulation (recovery time constant τ = 3.7 ± 2.1 min) as well as investigation of an effect of various chemicals (e.g., KCl) on all selected parameters. The experiments endorse characeaen algae as a model system to be routinely explored in education of biophysics and bioelectrical phenomena of the cell.

Strength Training Increases Conduction Velocity of High-Threshold Motor Units.

Motor unit conduction velocity (MUCV) represents the propagation velocity of action potentials along the muscle fibers innervated by individual motor neurons and indirectly reflects the electrophysiological properties of the sarcolemma. In this study, we investigated the effect of a 4-wk strength training intervention on the peripheral properties (MUCV and motor unit action potential amplitude, RMSMU) of populations of longitudinally tracked motor units (MU). The adjustments exhibited by 12 individuals who participated in the training (INT) were compared with 12 controls (CON). Strength training involved ballistic (4 × 10) and sustained (3 × 10) isometric ankle dorsiflexions. Measurement sessions involved the recordings of maximal voluntary isometric force and submaximal isometric ramp contractions, whereas high-density surface EMG was recorded from the tibialis anterior. High-density surface EMG signals were decomposed into individual MU discharge timings, and MU was tracked across the intervention. Maximal voluntary isometric force (+14.1%, P = 0.003) and average MUCV (+3.0%, P = 0.028) increased in the INT group, whereas normalized MU recruitment threshold (RT) decreased (-14.9%, P = 0.001). The slope (rate of change) of the regression between MUCV and MU RT increased only in the INT group (+32.6%, P = 0.028), indicating a progressive greater increase in MUCV for higher-threshold MU. The intercept (initial value) of MUCV did not change after the intervention (P = 0.568). The association between RMSMU and MU RT was not altered by the training. The increase in the rate of change in MUCV as a function of MU RT, but not the initial value of MUCV, suggests that short-term strength training elicits specific adaptations in the electrophysiological properties of the muscle fiber membrane in high-threshold MU.

F98. Enhanced muscle evaluation using a novel impedance-electromyography (I-EMG) needle electrode

Introduction A wealth of advantages has made needle electromyography (EMG) the standard, “go-to” clinical test used to evaluate muscle disorders. Nevertheless, EMG has associated technological limitations. For example, EMG only characterizes muscles’ active electrical activity, namely the depolarization of myofibers’ membrane. While clearly valuable, EMG does not provide information about non-electrically active (i.e. passive) properties altered in diseased muscle, the data’s being secondary to these alterations. One example of the relationship between passive and active electrical properties of muscle are the membrane resistance Rm (passive) and the membrane capacitance Cm (passive) of myofibers which determine the propagation velocity of action potentials (active). To date, measuring in vivo Rm, Cm and EMG using the same needle electrode was not possible. Methods We created a novel needle electrode integrating impedance and EMG technologies with the capability to measure simultaneously both passive (impedance) and active (EMG) electrical properties of muscle. We then conducted in vivo measurements in five C57BL/6 J wild-type mice at 6 weeks of age (The Jackson Lab, Bar Harbor, ME). Recordings were made in the gastrocnemius muscle with the animals mildly sedated (isoflurane 0.5–1% delivered by nosecone) while providing gentle stimuli to the hind limbs such that the animals repeatedly withdrew the limb. Results With our device, we were able to detect synchronized reductions in Rm and Cm with EMG activation. Rm is the inverse of the myofiber permeability; the higher the permeability, the lower Rm and vice versa. Cm is the ability of myofibers to store electrical charge. This result indicates the possibility to detect real-time passive and active electrical changes of myofibers during activity, which can provide additional information to help with the diagnosis. Conclusion Impedance technology embedded into an EMG needle electrode can greatly extend the diagnostic capabilities of needle EMG technology. Needle I-EMG could serve as a new bedside tool to assess muscle condition without increasing the complexity or duration of the standard needle EMG. Identifying changes in membrane properties of myofibers could serve as a convenient tool to assist with primary diagnosis or the impact of the therapies in a variety of conditions, including the denervating conditions and myotonic disorders.

Multiple targets for flecainide action: implications for cardiac arrhythmogenesis.

This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues

We investigated whether the developmental stage of mouse cardiac fibroblasts (CFs) influences the formation and function of engineered cardiac tissues made of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs). Engineered cardiac tissue patches were fabricated by encapsulating pure mESC-CMs, mESC-CMs + adult CFs, or mESC-CMs + fetal CFs in fibrin-based hydrogel. Tissue patches containing fetal CFs exhibited higher velocity of action potential propagation and contractile force amplitude compared to patches containing adult CFs, while pure mESC-CM patches did not form functional syncytium. The functional improvements in mESC-CM + fetal CF patches were associated with differences in structural remodeling and increased expression of proteins involved in cardiac function. To determine role of paracrine signaling, we cultured pure mESC-CMs within miniature tissue “micro-patches” supplemented with media conditioned by adult or fetal CFs. Fetal CF-conditioned media distinctly enhanced CM spreading and contractile activity, which was shown by pathway inhibitor experiments and Western blot analysis to be mediated via MEK-ERK signaling. In mESC-CM monolayers, CF-conditioned media did not alter CM spreading or MEK-ERK activation. Collectively, our studies show that 3D co-culture of mESC-CMs with embryonic CFs is superior to co-culture with adult CFs for in vitro generation of functional myocardium. Ensuring consistent developmental stages of cardiomyocytes and supporting non-myocytes may be a critical factor for promoting functional maturation of engineered cardiac tissues.

Predicting electromyographic signals under realistic conditions using a multiscale chemo-electro-mechanical finite element model.

This paper presents a novel multiscale finite element-based framework for modelling electromyographic (EMG) signals. The framework combines (i) a biophysical description of the excitation-contraction coupling at the half-sarcomere level, (ii) a model of the action potential (AP) propagation along muscle fibres, (iii) a continuum-mechanical formulation of force generation and deformation of the muscle, and (iv) a model for predicting the intramuscular and surface EMG. Owing to the biophysical description of the half-sarcomere, the model inherently accounts for physiological properties of skeletal muscle. To demonstrate this, the influence of membrane fatigue on the EMG signal during sustained contractions is investigated. During a stimulation period of 500 ms at 100 Hz, the predicted EMG amplitude decreases by 40% and the AP propagation velocity decreases by 15%. Further, the model can take into account contraction-induced deformations of the muscle. This is demonstrated by simulating fixed-length contractions of an idealized geometry and a model of the human tibialis anterior muscle (TA). The model of the TA furthermore demonstrates that the proposed finite element model is capable of simulating realistic geometries, complex fibre architectures, and can include different types of heterogeneities. In addition, the TA model accounts for a distributed innervation zone, different fibre types and appeals to motor unit discharge times that are based on a biophysical description of the α motor neurons.

Velocity Selective Neural Signal Recording Using a Space-Time Electrode Array.

Extracting the activity of a particular neural fiber from the extracellular recording of a peripheral nerve is quite important from different clinical perspectives. While traditional neural recording methods are unable to provide such granularity, new signal recording and processing techniques have offered promising solutions recently. A multi-electrode cuff in conjunction with a delay and sum beamforming structure has been used to detect the activity of different fibers in a nerve based on the propagation velocity of action potentials. However, as it is shown in this paper, simple delay and sum beamforming method encounters severe selectivity problem and signal distortion especially at higher velocities. In addition to scrutinizing the performance of the delay and sum beamformer and its inherent problems, here we propose a new beamforming method, based on broadband sensor array signal processing techniques, which exhibits much better selectivity with uniform frequency-velocity response. Our simulation results show how the new method can faithfully extract individual neural fiber activities and explore potential applications which could emerge from using such technique.

Saltatory conduction in unmyelinated axons: clustering of Na(+) channels on lipid rafts enables micro-saltatory conduction in C-fibers.

The action potential (AP), the fundamental signal of the nervous system, is carried by two types of axons: unmyelinated and myelinated fibers. In the former the action potential propagates continuously along the axon as established in large-diameter fibers. In the latter axons the AP jumps along the nodes of Ranvier—discrete, anatomically specialized regions which contain very high densities of sodium ion (Na+) channels. Therefore, saltatory conduction is thought as the hallmark of myelinated axons, which enables faster and more reliable propagation of signals than in unmyelinated axons of same outer diameter. Recent molecular anatomy showed that in C-fibers, the very thin (0.1 μm diameter) axons of the peripheral nervous system, Nav1.8 channels are clustered together on lipid rafts that float in the cell membrane. This localized concentration of Na+ channels resembles in structure the ion channel organization at the nodes of Ranvier, yet it is currently unknown whether this translates into an equivalent phenomenon of saltatory conduction or related-functional benefits and efficiencies. Therefore, we modeled biophysically realistic unmyelinated axons with both conventional and lipid-raft based organization of Na+ channels. We find that APs are reliably conducted in a micro-saltatory fashion along lipid rafts. Comparing APs in unmyelinated fibers with and without lipid rafts did not reveal any significant difference in either the metabolic cost or AP propagation velocity. By investigating the efficiency of AP propagation over Nav1.8 channels, we find however that the specific inactivation properties of these channels significantly increase the metabolic cost of signaling in C-fibers.

Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing

Mechanical stretch of cardiac muscle modulates action potential propagation velocity, causing potentially arrhythmogenic conduction slowing. The mechanisms by which stretch alters cardiac conduction remain unknown, but previous studies suggest that stretch can affect the conformation of caveolae in myocytes and other cell types. We tested the hypothesis that slowing of action potential conduction due to cardiac myocyte stretch is dependent on caveolae.Cardiac action potential propagation velocities, measured by optical mapping in isolated mouse hearts and in micropatterned mouse cardiomyocyte cultures, decreased reversibly with volume loading or stretch, respectively (by 19±5% and 26±4%). Stretch-dependent conduction slowing was not altered by stretch-activated channel blockade with gadolinium or by GsMTx-4 peptide, but was inhibited when caveolae were disrupted via genetic deletion of caveolin-3 (Cav3 KO) or membrane cholesterol depletion by methyl-β-cyclodextrin. In wild-type mouse hearts, stretch coincided with recruitment of caveolae to the sarcolemma, as observed by electron microscopy. In myocytes from wild-type but not Cav3 KO mice, stretch significantly increased cell membrane capacitance (by 98±64%), electrical time constant (by 285±149%), and lipid recruitment to the bilayer (by 84±39%).Recruitment of caveolae to the sarcolemma during physiologic cardiomyocyte stretch slows ventricular action potential propagation by increasing cell membrane capacitance.

Intra-cortical propagation of EEG alpha oscillations

The most salient feature of spontaneous human brain activity as recorded with electroencephalography (EEG) are rhythmic fluctuations around 10Hz. These alpha oscillations have been reported to propagate over the scalp with velocities in the range of 5–15m/s. Since these velocities are in the range of action potential velocities through cortico-cortical axons, it has been hypothesized that the observed scalp waves reflect cortico-cortically mediated propagation of cortical oscillations. The reported scalp velocities however, appear to be inconsistent with those estimated from local field potential recordings in dogs, which are <1m/s and agree with the propagation velocity of action potentials in intra-cortical axons. In this study, we resolve these diverging findings using a combination of EEG data-analysis and biophysical modeling. In particular, we demonstrate that the observed scalp velocities can be accounted for by slow traveling oscillations, which provides support for the claim that spatial propagation of alpha oscillations is mediated by intra-cortical axons.

Ionic mechanisms of action potential propagation velocity changes in peripheral C-fibers. Implications for pain

Ionic mechanisms of action potential propagation velocity changes in peripheral C-fibers. Implications for pain

Simulation of action potential propagation in plants

Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H +-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H +-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity.

Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function

Recent advances in pluripotent stem cell research have provided investigators with potent sources of cardiogenic cells. However, tissue engineering methodologies to assemble cardiac progenitors into aligned, 3-dimensional (3D) myocardial tissues capable of physiologically relevant electrical conduction and force generation are lacking. In this study, we introduced 3D cell alignment cues in a fibrin-based hydrogel matrix to engineer highly functional cardiac tissues from genetically purified mouse embryonic stem cell-derived cardiomyocytes (CMs) and cardiovascular progenitors (CVPs). Procedures for CM and CVP derivation, purification, and functional differentiation in monolayer cultures were first optimized to yield robust intercellular coupling and maximize velocity of action potential propagation. A versatile soft-lithography technique was then applied to reproducibly fabricate engineered cardiac tissues with controllable size and 3D architecture. While purified CMs assembled into a functional 3D syncytium only when supplemented with supporting non-myocytes, purified CVPs differentiated into cardiomyocytes, smooth muscle, and endothelial cells, and autonomously supported the formation of functional cardiac tissues. After a total culture time similar to period of mouse embryonic development (21 days), the engineered cardiac tissues exhibited unprecedented levels of 3D organization and functional differentiation characteristic of native neonatal myocardium, including: 1) dense, uniformly aligned, highly differentiated and electromechanically coupled cardiomyocytes, 2) rapid action potential conduction with velocities between 22 and 25 cm/s, and 3) significant contractile forces of up to 2 mN. These results represent an important advancement in stem cell-based cardiac tissue engineering and provide the foundation for exploiting the exciting progress in pluripotent stem cell research in the future tissue engineering therapies for heart disease.

An analysis of the relationships between subthreshold electrical properties and excitability in skeletal muscle

Skeletal muscle activation requires action potential (AP) initiation followed by its sarcolemmal propagation and tubular excitation to trigger Ca2+ release and contraction. Recent studies demonstrate that ion channels underlying the resting membrane conductance (GM) of fast-twitch mammalian muscle fibers are highly regulated during muscle activity. Thus, onset of activity reduces GM, whereas prolonged activity can markedly elevate GM. Although these observations implicate GM regulation in control of muscle excitability, classical theoretical studies in un-myelinated axons predict little influence of GM on membrane excitability. However, surface membrane morphologies differ markedly between un-myelinated axons and muscle fibers, predominantly because of the tubular (t)-system of muscle fibers. This study develops a linear circuit model of mammalian muscle fiber and uses this to assess the role of subthreshold electrical properties, including GM changes during muscle activity, for AP initiation, AP propagation, and t-system excitation. Experimental observations of frequency-dependent length constant and membrane-phase properties in fast-twitch rat fibers could only be replicated by models that included t-system luminal resistances. Having quantified these resistances, the resulting models showed enhanced conduction velocity of passive current flow also implicating elevated AP propagation velocity. Furthermore, the resistances filter passive currents such that higher frequency current components would determine sarcolemma AP conduction velocity, whereas lower frequency components excite t-system APs. Because GM modulation affects only the low-frequency membrane impedance, the GM changes in active muscle would predominantly affect neuromuscular transmission and low-frequency t-system excitation while exerting little influence on the high-frequency process of sarcolemmal AP propagation. This physiological role of GM regulation was increased by high Cl− permeability, as in muscle endplate regions, and by increased extracellular [K+], as observed in working muscle. Thus, reduced GM at the onset of exercise would enhance t-system excitation and neuromuscular transmission, whereas elevated GM after sustained activity would inhibit these processes and thereby accentuate muscle fatigue.

Organization of Anti-Phase Synchronization Pattern in Neural Networks: What are the Key Factors?

Anti-phase oscillation has been widely observed in cortical neural network. Elucidating the mechanism underlying the organization of anti-phase pattern is of significance for better understanding more complicated pattern formations in brain networks. In dynamical systems theory, the organization of anti-phase oscillation pattern has usually been considered to relate to time delay in coupling. This is consistent to conduction delays in real neural networks in the brain due to finite propagation velocity of action potentials. However, other structural factors in cortical neural network, such as modular organization (connection density) and the coupling types (excitatory or inhibitory), could also play an important role. In this work, we investigate the anti-phase oscillation pattern organized on a two-module network of either neuronal cell model or neural mass model, and analyze the impact of the conduction delay times, the connection densities, and coupling types. Our results show that delay times and coupling types can play key roles in this organization. The connection densities may have an influence on the stability if an anti-phase pattern exists due to the other factors. Furthermore, we show that anti-phase synchronization of slow oscillations can be achieved with small delay times if there is interaction between slow and fast oscillations. These results are significant for further understanding more realistic spatiotemporal dynamics of cortico-cortical communications.

Motor Unit Conduction Velocity during Sustained Contraction after Eccentric Exercise

Eccentric contractions induce muscle fiber damage that is associated with a decreased capacity to generate voluntary force and increased fiber membrane permeability. Changes in fiber membrane permeability results in cell depolarization that is expected to have an effect on the action potential propagation velocity of the muscle fibers. The aim of the study was to investigate the action potential propagation velocity in individual motor units before and 24 and 48 h after eccentric exercise. Multichannel surface and fine-wire intramuscular EMG signals were concurrently recorded from two locations of the right vastus medialis muscle of 10 healthy men during 60-s isometric contractions at 10% and 30% of the maximal force. The maximal force decreased by 26.1 ± 16.1% (P < 0.0001) at 24 h and remained reduced by 23.6 ± 14.5% (P < 0.0001) 48 h after exercise with respect to baseline. With respect to baseline, motor unit conduction velocity decreased (P < 0.05) by (average over 24 and 48 h after exercise) 7.7 ± 2.7% (10% maximal voluntary contraction (MVC), proximal), 7.2 ± 2.8% (10% MVC, distal), 8.6 ± 3.8% (30% MVC, proximal), and 6.2 ± 1.5% (30% MVC, distal). Moreover, motor unit conduction velocity decreased over time during the sustained contractions at faster rates when assessed 24 and 48 h after exercise with respect to baseline for both contraction forces and locations (P < 0.05). These results indicate that the electrophysiological membrane properties of muscle fibers are altered by exercise-induced muscle fiber damage.