Area under the curve and amplitude of the compound motor action potential are clinically interchangeable quantitative measures of neuromuscular block: a method comparison study.

Background: Current guidelines recommend quantitative neuromuscular block monitoring during neuromuscular blocking agent administration. Monitors using surface electromyography (EMG) determine compound motor action potential (cMAP) amplitude or area under the curve (AUC). Rigorous evaluation of the interchangeability of these methods is lacking but necessary for clinical and research assurance that EMG interpretations of the depth of neuromuscular block are not affected by the methodology. Methods: Digitised EMG waveforms were studied from 48 patients given rocuronium during two published studies. The EMG amplitudes and AUCs were calculated pairwise from all cMAPs classified as valid by visual inspection. Ratios of the first twitch (T1) to the control T1 before administration of rocuronium (T1c) and train-of-four ratios (TOFRs) were compared using repeated measures Bland-Altman analysis. Results: Among the 2419 paired T1/T1c differences where the average T1/T1c was ≤0.2, eight (0.33%) were outside prespecified clinical limits of agreement (-0.148 to 0.164). Among the 1781 paired TOFR differences where the average TOFR was ≥0.8, 70 (3.93%) were outside the prespecified clinical limits of agreement ((-0.109 to 0.134). Among all 7286 T1/T1c paired differences, the mean bias was 0.32 (95% confidence interval 0.202-0.043), and among all 5559 paired TOFR differences, the mean bias was 0.011 (95% confidence interval 0.0050-0.017). Among paired T1/T1c and TOFR differences, Lin's concordance correlation coefficients were 0.98 and 0.995, respectively. Repeatability coefficients for T1/T1c and TOFR were <0.08, with no differences between methods. Conclusions: Quantitative assessment neuromuscular block depth is clinically interchangeable when calculated using cMAP amplitude or the AUC.

Alzheimer's-linked axonal changes accompany elevated antidromic action potential failure rate in aged mice.

Alzheimer's disease (AD) affects both grey and white matter (WM), but considerably more is known about the former. Interestingly, WM disruption has been consistently observed and thoroughly described using imaging modalities, particularly MRI which has shown WM functional disconnections between the hippocampus and other brain regions during AD pathogenesis when early neurodegeneration and synapse loss are also evident. Nonetheless, high-resolution structural and functional analyses of WM during AD pathogenesis remain scarce. Given the importance of the myelinated axons in the WM for conveying information across brain regions, such studies will provide valuable information on the cellular drivers and consequences of WM disruption that contribute to the characteristic cognitive decline of AD. Here, we employed a multi-scale approach to investigate hippocampal WM disruption during AD pathogenesis and determine whether hippocampal WM changes accompany the well-documented grey matter losses. Our data indicate that ultrastructural myelin disruption is elevated in the alveus in human AD cases and increases with age in 5xFAD mice. Unreliable action potential propagation and changes to sodium channel expression at the node of Ranvier co-emerged with this deterioration. These findings provide important insight to the neurobiological substrates and functional consequences of decreased WM integrity and are consistent with the notion that hippocampal disconnection contributes to cognitive changes in AD.

Creating Computational Models of Ion Channel Dynamics.

Markov models are widely used to represent ion channel protein configurations as different states in the model's topology. Such models allow for dynamic simulation of ion channel kinetics through the simulated application of voltage potentials across a cell membrane. In this chapter, we present a general method for creating Markov models of ion channel kinetics using computational optimization alongside a fully featured example model of a cardiac potassium channel. Our methods cover designing training protocols, iteratively testing potential model topologies for structure identification, creation of algorithms for model simulation, as well as methods for assessing the quality of fit for a finalized model.

Anti-Arrhythmic Mechanisms of Epidural Blockade After Myocardial Infarction.

BACKGROUND: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachycardia in small case series of patients with refractory ventricular tachycardia and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear, and its use after myocardial infarction is limited by concerns for potential right ventricular dysfunction. METHODS: Myocardial infarction was created in Yorkshire pigs (N=22) by left anterior descending coronary artery occlusion. Six weeks after myocardial infarction, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. Right and left ventricular hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity and intrinsic cardiac neural activity, and ventricular effective refractory periods and slope of restitution (Smax) were assessed before and after TEA. Ventricular tachyarrhythmia inducibility was assessed by programmed electrical stimulation. RESULTS: TEA reduced inducibility of ventricular tachyarrhythmias by 70%. TEA did not affect right ventricular-systolic pressure or contractility although left ventricular-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular effective refractory periods prolonged significantly at critical sites of arrhythmogenesis, and Smax was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both baroreflex sensitivity and intrinsic cardiac neural activity. CONCLUSIONS: TEA does not compromise right ventricular function in infarcted hearts. Its antiarrhythmic mechanisms are mediated by increases in ventricular effective refractory period and ARIs, decreases in Smax, and reductions in border zone electrophysiological heterogeneities. TEA improves parasympathetic function, which may independently underlie some of its observed antiarrhythmic mechanisms. This study provides novel insights into the antiarrhythmic mechanisms of TEA while highlighting its applicability to the clinical setting.

Can Plants Perceive Human Gestures? Using AI to Track Eurythmic Human-Plant Interaction.

This paper explores if plants are capable of responding to human movement by changes in their electrical signals. Toward that goal, we conducted a series of experiments, where humans over a period of 6 months were performing different types of eurythmic gestures in the proximity of garden plants, namely salad, basil, and tomatoes. To measure plant perception, we used the plant SpikerBox, which is a device that measures changes in the voltage differentials of plants between roots and leaves. Using machine learning, we found that the voltage differentials over time of the plant predict if (a) eurythmy has been performed, and (b) which kind of eurythmy gestures has been performed. We also find that the signals are different based on the species of the plant. In other words, the perception of a salad, tomato, or basil might differ just as perception of different species of animals differ. This opens new ways of studying plant ecosystems while also paving the way to use plants as biosensors for analyzing human movement.

Pacemaker Channels and the Chronotropic Response in Health and Disease.

Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of cardiovascular disease-including ischemic heart disease, heart failure, and arrhythmias. While the clinical significance of regulating changes in heart rate, known as the chronotropic effect, is undeniable, the mechanisms controlling these changes remain not fully understood. Heart rate acceleration and deceleration are mediated by increasing or decreasing the spontaneous firing rate of pacemaker cells in the sinoatrial node. During the transition from rest to activity, sympathetic neurons stimulate these cells by activating ß-adrenergic receptors and increasing intracellular cyclic adenosine monophosphate. The same signal transduction pathway is targeted by positive chronotropic drugs such as norepinephrine and dobutamine, which are used in the treatment of cardiogenic shock and severe heart failure. The cyclic adenosine monophosphate-sensitive hyperpolarization-activated current (If) in pacemaker cells is passed by hyperpolarization-activated cyclic nucleotide-gated cation channels and is critical for generating the autonomous heartbeat. In addition, this current has been suggested to play a central role in the chronotropic effect. Recent studies demonstrate that cyclic adenosine monophosphate-dependent regulation of HCN4 (hyperpolarization-activated cyclic nucleotide-gated cation channel isoform 4) acts to stabilize the heart rate, particularly during rapid rate transitions induced by the autonomic nervous system. The mechanism is based on creating a balance between firing and recently discovered nonfiring pacemaker cells in the sinoatrial node. In this way, hyperpolarization-activated cyclic nucleotide-gated cation channels may protect the heart from sinoatrial node dysfunction, secondary arrhythmia of the atria, and potentially fatal tachyarrhythmia of the ventricles. Here, we review the latest findings on sinoatrial node automaticity and discuss the physiological and pathophysiological role of HCN pacemaker channels in the chronotropic response and beyond.

Determining the Optimal Position of Surface Electrodes for Diaphragm Electromyography: A Cross-Sectional Study.

BACKGROUND: Placing electrodes on different aspects of the chest determines the motor firing from the diaphragm. The electrode placement close to the extent of the muscle gave promising readings as compared to the ones that were placed away. The position with the maximum amplitude and least duration was chosen. Positions of the electrodes were decided as per the extent of the muscle. The aim is to determine the appropriate position of surface electrodes for surface diaphragm electromyography (EMG). MATERIAL AND METHODOLOGY: Thirty healthy individuals of age ranging from 21 to 45 years were included in the study. Participants were made to lie down in a supine position and different positions like G1 (recording electrode) 5 cm superior to the tip of the xiphoid process and G2 (reference) 16 cm along the costal margin from G1, G1 over the xiphoid tip and G2 at the seventh intercostal space at the costochondral junction and G1 over the xiphoid tip and G2 at the eight intercostal space at the costochondral junction were used for assessing maximum amplitudes and durations were observed by using a Octopus New Wave EMG machine (Octopus Medical Technologies, Vadodara, IND). After observing all the positions, an optimum position for maximum amplitude and least duration was analyzed. RESULTS: As per the study, out of the four positions, the electrode placements on the tip of the xiphoid process and 16 cm away diagonally on the sixth intercostal space showed maximum amplitude and the least duration with maximum mean amplitude and less mean duration of 232.35 and 7.316. On the seventh intercostal space it was 199.15 and 7.887 and on the eighth intercostal space was 176.055 and 8.639. The tip of the xiphoid process and 16 cm away diagonally on the sixth intercostal space is chosen as the appropriate position for electrode placement for EMG of the diaphragm. CONCLUSION: We conclude that the best electrode position was when the electrodes were placed 5 cm superior to the xiphoid process, i.e., G1, and 16 cm away from the recording electrode on the costochondral junction, i.e., G2, at the sixth intercostal space. Ground electrode placement is the nearest bony prominence, i.e., xiphisternum.

Toluene alters the intrinsic excitability and excitatory synaptic transmission of basolateral amygdala neurons.

Introduction: Inhalant abuse is an important health issue especially among children and adolescents who often encounter these agents in the home. Research into the neurobiological targets of inhalants has lagged behind that of other drugs such as alcohol and psychostimulants. However, studies from our lab and others have begun to reveal how inhalants such as the organic solvent toluene affect neurons in key addiction related areas of the brain including the ventral tegmental area, nucleus accumbens and medial prefrontal cortex. In the present study, we extend these findings and examine the effect of toluene on electrophysiological responses of pyramidal neurons in the basolateral amygdala BLA, a region important for generating emotional and reward based information needed to guide future behavior. Methods: Whole-cell patch-clamp electrophysiology recordings of BLA pyramidal neurons in rat brain slices were used to assess toluene effects on intrinsic excitability and excitatory glutamatergic synaptic transmission. Results: Acute application of 3 mM but not 0.3 mM toluene produced a small but significant (~20%) increase in current-evoked action potential (AP) firing that reversed following washout of the toluene containing solution. The change in firing during exposure to 3 mM toluene was accompanied by selective changes in AP parameters including reduced latency to first spike, increased AP rise time and decay and a reduction in the fast after-hyperpolization. To examine whether toluene also affects excitatory synaptic signaling, we expressed channelrhodopsin-2 in medial prefrontal cortex neurons and elicited synaptic currents in BLA neurons via light pulses. Toluene (3 mM) reduced light-evoked AMPA-mediated synaptic currents while a lower concentration (0.3 mM) had no effect. The toluene-induced reduction in AMPA-mediated BLA synaptic currents was prevented by the cannabinoid receptor-1 antagonist AM281. Discussion: These findings are the first to demonstrate effects of acute toluene on BLA pyramidal neurons and add to existing findings showing that abused inhalants such as toluene have significant effects on neurons in brain regions involved in natural and drug induced reward.

Discovering optimal features for neuron-type identification from extracellular recordings.

Advancements in multichannel recordings of single-unit activity (SUA) in vivo present an opportunity to discover novel features of spatially-varying extracellularly-recorded action potentials (EAPs) that are useful for identifying neuron-types. Traditional approaches to classifying neuron-types often rely on computing EAP waveform features based on conventions of single-channel recordings and thus inherit their limitations. However, spatiotemporal EAP waveforms are the product of signals from underlying current sources being mixed within the extracellular space. We introduce a machine learning approach to demix the underlying sources of spatiotemporal EAP waveforms. Using biophysically realistic computational models, we simulate EAP waveforms and characterize them by the relative prevalence of these sources, which we use as features for identifying the neuron-types corresponding to recorded single units. These EAP sources have distinct spatial and multi-resolution temporal patterns that are robust to various sampling biases. EAP sources also are shared across many neuron-types, are predictive of gross morphological features, and expose underlying morphological domains. We then organize known neuron-types into a hierarchy of latent morpho-electrophysiological types based on differences in the source prevalences, which provides a multi-level classification scheme. We validate the robustness, accuracy, and interpretations of our demixing approach by analyzing simulated EAPs from morphologically detailed models with classification and clustering methods. This simulation-based approach provides a machine learning strategy for neuron-type identification.

Using Compound Neural Action Potentials for Functional Validation of a High-Density Intraneural Interface: A Preliminary Study.

Compound nerve action potentials (CNAPs) were used as a metric to assess the stimulation performance of a novel high-density, transverse, intrafascicular electrode in rat models. We show characteristic CNAPs recorded from distally implanted cuff electrodes. Evaluation of the CNAPs as a function of stimulus current and calculation of recruitment plots were used to obtain a qualitative approximation of the neural interface's placement and orientation inside the nerve. This method avoids elaborate surgeries required for the implantation of EMG electrodes and thus minimizes surgical complications and may accelerate the healing process of the implanted subject.

A systematic review of the association between the age of onset of spinal bulbar muscular atrophy (Kennedy's disease) and the length of CAG repeats in the androgen receptor gene.

Introduction: Spinal bulbar muscular atrophy (SBMA) is an X-linked recessive motor neuron disorder caused by the presence of ≥38 CAG repeats in the androgen receptor gene. Existing literature indicates a relationship between CAG repeat number and the onset age of some motor symptoms of SBMA. This review explores the effect of larger versus shorter CAG repeats on the age of weakness onset in male SBMA patients. Methods: Three databases (October 2021; MEDLINE, SCOPUS, and Web of Science), Cambridge University Press, and Annals of Neurology were searched. 514 articles were initially identified, of which 13 were included for qualitative synthesis. Results: Eleven of the thirteen articles identified a statistically significant inverse correlation between CAG repeat length and age of weakness onset in SBMA. Five studies indicated that SBMA patients with between 35 and 37 CAG repeats had an older age of weakness onset than patients with over 40 CAG repeats. The minimum number of CAG repeats associated with weakness was in the mid-to-late thirties. Conclusion: Identification of a relationship between CAG repeat number and age of weakness may enable earlier detection and intervention for SBMA. In the future, studies should use interviews, chart reviews, and standardized scoring methods to reduce effects of retrospective bias.

Somatic ion channels and action potentials in olfactory receptor cells and vomeronasal receptor cells.

Olfactory receptor cells are primary sensory neurons that catch odor molecules in the olfactory system, and vomeronasal receptor cells catch pheromones in the vomeronasal system. When odor or pheromone molecules bind to receptor proteins expressed on the membrane of the olfactory cilia or vomeronasal microvilli, receptor potentials are generated in their receptor cells. This initial excitation is transmitted to the soma via dendrites, and action potentials are generated in the soma and/or axon and transmitted to the central nervous system. Thus, olfactory and vomeronasal receptor cells play an important role in converting chemical signals into electrical signals. In this review, the electrophysiological characteristics of ion channels in the somatic membrane of olfactory receptor cells and vomeronasal receptor cells in various species are described and the differences between the action potential dynamics of olfactory receptor cells and vomeronasal receptor cells are compared.

Unveiling the Effects of Left Hemispheric Intracerebral Hemorrhage on Long-term Potentiation and Inflammation in the Bilateral Hippocampus: A Preclinical Study.

OBJECTIVE: Changes in cognition and memory are common complications of intracerebral hemorrhage (ICH), although the exact cause of this phenomenon is still unknown. The objectives of our project were to assess the changes in long-term potentiation, inflammation, and cell damage in the bilateral hippocampus following striatal intracerebral hemorrhage at different time points. MATERIALS AND METHODS: Unilateral ICH was induced in the striatum of 96 Wistar rats (6 control groups and 6 ICH groups). We measured changes in synaptic inputs in the bilateral hippocampus using the field potential recording method on days 3, 7, and 14 after ICH. After staining the section with hematoxylin, the volume and number of hippocampal cells were measured. The number of NF-κB positive cells was evaluated using the immunohistochemistry method. RESULTS: There was a significant change in the amplitude and slope of the hippocampal excitatory potential in the ICH group compared to the sham group, but only on the 7th day after surgery. Specifically, the ipsilateral hippocampus in the ICH-7 group showed an increase in stimulation recording in 90 minutes compared to the sham-7 group (p<0.0001), while the contralateral hippocampus in the ICH-7 group exhibited a decrease in potential recording compared to the sham-7 group (p<0.0001). By day 14, the ICH group had a lower cell density in both the ipsilateral (p<0.05) and contralateral hippocampus (p<0.05) compared to the sham group, but there was no significant change in the hippocampal volume between the groups at any time interval. Furthermore, our immunohistochemical analysis revealed that the number of NF-kB-positive cells in both hemispheres of the ICH groups was significantly greater than that of the sham groups across all time intervals. CONCLUSIONS: These findings suggest that striatal injury may lead to inflammation and cell death in the bilateral hippocampus, which can impair cognitive function after ICH.

ART and AutoART ECAP measurements and cochlear nerve anatomy as predictors in adult cochlear implant recipients.

PURPOSE: The purpose of this retrospective study is to compare the results of electrically evoked compound action potential (ECAP) measurements using automatic auditory response telemetry (AutoART) with those obtained by ART in adults. The study also aimed to evaluate the predictive value of intraoperative ART and AutoART ECAPs for speech intelligibility (SI) and hearing success (HS), and to determine if cochlear nerve (CN) cross-sectional area (CSA) obtained preoperatively by magnetic resonance imaging (MRI) scans could predict ART and AutoART ECAPs and SI and HS outcome. METHODS: The study analyzed and correlated ART and AutoART ECAP thresholds at electrodes E2, E6, and E10, as well as averaged ECAP thresholds over electrodes E1-E12, using data from 32 implants. Correlations were also examined for ART and AutoART ECAP slopes. In addition, averaged ART and AutoART ECAP thresholds and slopes over all 12 electrodes for each participant were correlated with CN CSA measured from MRI sequences. SI of the monosyllabic Freiburg Speech Test at 65 dB sound pressure level was examined along with averaged ART and AutoART thresholds and slopes over all 12 electrodes. A parallel analysis was performed for HS, derived from the difference between baseline and 6-month SI. Finally, correlations between CN CSA and SI, as well as CN CSA and HS were examined. RESULTS: The results of the study showed a significant positive correlation between ART and AutoART ECAP thresholds and as well as slopes for E2, E6, E10 and averaged thresholds and slopes of E1-E12. However, no significant correlation was observed between ART and AutoART averaged ECAP thresholds and slopes and either SI and HS or CN CSA. Furthermore, no significant correlation was found between CN CSA and SI and HS. CONCLUSION: While AutoART is a reliable and safe program for measuring ECAPs in adults, the study found no preoperative prognostic information on intraoperative ECAP results using parameters extracted from current MRI sequences or pre-/intraoperative information on subsequent hearing outcome using ECAP and CN CSA.

Expression and electrophysiological characteristics of VGSC during mouse myoblasts differentiation.

Voltage-gated sodium channels (VGSC) are essential for triggering and relaying action potentials (AP), which perform critical functions in a variety of physiological processes, such as controlling muscle contractions and facilitating the release of neurotransmitters. In this study, we used a mouse C2C12 cell differentiation model to study the molecular expression and channel dynamics of VGSC and to investigate the exact role of VGSC in the development of muscle regeneration. Immunofluorescence, Real-time quantitative polymerase chain reaction, Western blot, and whole-cell patch clamp were employed for this purpose in mouse myoblasts. The findings revealed an increase in intracellular sodium concentration, NaV1.4 gene expression, and protein expression with the progress of differentiation (days 0, 1, 3, 5 and 7). Furthermore, VGSC dynamics exhibit the following characteristics: ① The increase of sodium current (INa); ② The decrease in the activation threshold and the voltage trigger maximum of INa; ③ A positive shift in the steady-state inactivation curve; ④ The recovery of INa during repolarization is delayed, the activity-dependent decay rate of INa was accelerated, and the proportionate amount of the fraction of activated channels was reduced. Based on these results, it is postulated that the activation threshold of AP could be decreased, and the refractory period could be extended with the extension of differentiation duration, which may contribute to muscle contraction. Taken together, VGSC provides a theoretical and empirical basis for exploring potential targets for neuromuscular diseases and other therapeutic muscle regeneration dysfunctions.

Injection of IK1 through dynamic clamp can make all the difference in patch-clamp studies on hiPSC-derived cardiomyocytes.

Human-induced stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable tool for studying development, pharmacology, and (inherited) arrhythmias. Unfortunately, hiPSC-CMs are depolarized and spontaneously active, even the working cardiomyocyte subtypes such as atrial- and ventricular-like hiPSC-CMs, in contrast to the situation in the atria and ventricles of adult human hearts. Great efforts have been made, using many different strategies, to generate more mature, quiescent hiPSC-CMs with more close-to-physiological resting membrane potentials, but despite promising results, it is still difficult to obtain hiPSC-CMs with such properties. The dynamic clamp technique allows to inject a current with characteristics of the inward rectifier potassium current (IK1), computed in real time according to the actual membrane potential, into patch-clamped hiPSC-CMs during action potential measurements. This results in quiescent hiPSC-CMs with a close-to-physiological resting membrane potential. As a result, action potential measurements can be performed with normal ion channel availability, which is particularly important for the physiological functioning of the cardiac SCN5A-encoded fast sodium current (INa). We performed in vitro and in silico experiments to assess the beneficial effects of the dynamic clamp technique in dissecting the functional consequences of the SCN5A-1795insD+/- mutation. In two separate sets of patch-clamp experiments on control hiPSC-CMs and on hiPSC-CMs with mutations in ACADVL and GNB5, we assessed the value of dynamic clamp in detecting delayed afterdepolarizations and in investigating factors that modulate the resting membrane potential. We conclude that the dynamic clamp technique has highly beneficial effects in all of the aforementioned settings and should be widely used in patch-clamp studies on hiPSC-CMs while waiting for the ultimate fully mature hiPSC-CMs.

Artificial intelligence-based classification of motor unit action potentials in real-world needle EMG recordings.

OBJECTIVE: To develop an artificial neural network (ANN) for classification of motor unit action potential (MUAP) duration in real-word, unselected and uncleaned needle electromyography (n-EMG) recordings. METHODS: Two nested ANN models were trained, the first discerning muscle rest, contraction and artifacts in n-EMG recordings from 2674 individual muscles from 326 patients obtained as part of daily care. The second ANN model subsequently used segments labeled as contraction for prediction of prolonged, normal and shortened MUAPs. Model performance was assessed in one internal and two external validation datasets of 184, 30 and 50 muscles, respectively. RESULTS: The first model discerned rest, contraction and artifacts with an accuracy of 96%. The second model predicted prolonged, normal and shortened MUAPs with an accuracy of 67%, 83% and 68% in the different validation sets. CONCLUSIONS: We developed a two-step ANN that classifies rest, muscle contraction and artifacts from real-world n-EMG recordings with very high accuracy. MUAP duration classification had moderate accuracy. SIGNIFICANCE: This is the first study to show that an ANN can classify MUAPs in real-world n-EMG recordings highlighting the potential for AI assisted MUAP classification as a clinical tool.

Inhibitory Perturbations of Fluvastatin on Afterhyperpolarization Current, Erg-mediated K+ Current, and Hyperpolarization-activated Cation Current in Both Pituitary GH3 Cells and Primary Embryonic Mouse Cortical Neurons.

Fluvastatin (FLV), the first synthetically derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is a potent inhibitor of cholesterol biosynthesis. While its primary mechanism of action is to reduce cholesterol levels, there is some evidence suggesting that it may also have effects on K+ channels. However, the overall effects of fluvastatin on ionic currents are not yet well understood. The whole-cell clamp recordings were applied to evaluate the ionic currents and action potentials of cells. Here, we have demonstrated that FLV can effectively inhibit the amplitude of erg-mediated K+ current (IK(erg)) in pituitary tumor (GH3) cells, with an IC50 of approximately 3.2 µM. In the presence of FLV, the midpoint in the activation curve of IK(erg) was distinctly shifted to a less negative potential by 10 mV, with minimal modification of the gating charge. However, the magnitude of hyperpolarization-activated cation current (Ih) elicited by long-lasting membrane hyperpolarization was progressively decreased, with an IC50 value of 8.7 µM, upon exposure to FLV. More interestingly, we also found that FLV (5 µM) could regulate the action potential and afterhyperpolarization properties in primary embryonic mouse cortical neurons. Our study presents compelling evidence indicating that FLV has the potential to impact both the amplitude and gating of the ion channels IK(erg) and Ih. We also provide credible evidence suggesting that this drug has the potential to modify the properties of action potentials and the afterhyperpolarization current in electrically excitable cells. However, the assumption that these findings translate to similar in-vivo results remains unclear.

Larger and Denser: An Optimal Design for Surface Grids of EMG Electrodes to Identify Greater and More Representative Samples of Motor Units.

The spinal motor neurons are the only neural cells whose individual activity can be noninvasively identified. This is usually done using grids of surface electromyographic (EMG) electrodes and source separation algorithms; an approach called EMG decomposition. In this study, we combined computational and experimental analyses to assess how the design parameters of grids of electrodes influence the number and the properties of the identified motor units. We first computed the percentage of motor units that could be theoretically discriminated within a pool of 200 simulated motor units when decomposing EMG signals recorded with grids of various sizes and interelectrode distances (IEDs). Increasing the density, the number of electrodes, and the size of the grids, increased the number of motor units that our decomposition algorithm could theoretically discriminate, i.e., up to 83.5% of the simulated pool (range across conditions: 30.5-83.5%). We then identified motor units from experimental EMG signals recorded in six participants with grids of various sizes (range: 2-36 cm2) and IED (range: 4-16 mm). The configuration with the largest number of electrodes and the shortest IED maximized the number of identified motor units (56 ± 14; range: 39-79) and the percentage of early recruited motor units within these samples (29 ± 14%). Finally, the number of identified motor units further increased with a prototyped grid of 256 electrodes and an IED of 2 mm. Taken together, our results showed that larger and denser surface grids of electrodes allow to identify a more representative pool of motor units than currently reported in experimental studies.