Electrical Depolarization Research Articles

Unraveling Thermal Depolarization Phenomena in Biphasic Polarized Calcium Phosphate Catalyst

AbstractPermanently polarized biphasic calcium phosphate composed of hydroxyapatite and brushite (pp‐HAp/Bru), which is prepared by applying the thermally stimulated polarization treatment to calcined HAp, is used as a sustainable catalyst to transform CO2 into value‐added products. In this work, the stability of pp‐HAp/Bru is studied from structural, electrical, and catalytic perspectives, applying a thermal depolarization process with temperatures (Td) ranging from 200 to 1000 °C. Results show that the Bru phase is not stable when Td ≤ 400 °C, while the structure of the HAp refines and transforms into Bru when Td ≥ 600 °C. Besides, the electrical resistance and capacitance of the pp‐HAp/Bru increase with Td, evidencing the progressive electrical depolarization of the material. Thermal depolarization also influences the specific orientation of the OH– ions, which is partially lost (≈50%). All such changes affect the catalytic efficiency of pp‐HAp/Bru, which is proven using a reaction that transforms CO2 gas into acetic acid and formic acid. Results show that the total reaction yield linearly decreases with increasing Td. Based on such observations, a simple process is designed that allows the reconstitution of the structure and restores the activity of such green catalysts.

Cardiac Electromechanical Activity in Healthy Cats and Cats with Cardiomyopathies.

Optimal heart function depends on perfect synchronization between electrical and mechanical activity. In this pilot study, we aimed to investigate the electromechanical activity of the heart in healthy cats and cats with cardiomyopathy with phonocardiography (PCG) synchronized to an electrocardiography (ECG) pilot device. We included 29 cats (12 healthy cats and 17 cats diagnosed with cardiomyopathy) and performed a clinical examination, PCG synchronized with ECG and echocardiography. We measured the following durations with the pilot PCG device synchronized with ECG: QRS (ventricular depolarization), QT interval (electrical systole), QS1 interval (electromechanical activation time (EMAT)), S1S2 (mechanical systole), QS2 interval (electrical and mechanical systole) and electromechanical window (end of T wave to the beginning of S2). The measured parameters did not differ between healthy cats and cats with cardiomyopathy; however, in cats with cardiomyopathy, EMAT/RR, QS2/RR and S1S2/RR were significantly longer than in healthy cats. This suggests that the hypertrophied myocardium takes longer to generate sufficient pressure to close the mitral valve and that electrical systole, i.e., depolarization and repolarization, and mechanical systoles are longer in cats with cardiomyopathy. The PCG synchronized with the ECG pilot device proved to be a valuable tool for evaluating the electromechanical activity of the feline heart.

Physical Constraints in Intracellular Signaling: The Cost of Sending a Bit.

Many biological processes require timely communication between molecular components. Cells employ diverse physical channels to this end, transmitting information through diffusion, electrical depolarization, and mechanical waves among other strategies. Here we bound the energetic cost of transmitting information through these physical channels, in k_{B}T/bit, as a function of the size of the sender and receiver, their spatial separation, and the communication latency. These calculations provide an estimate for the energy costs associated with information processing arising from the physical constraints of the cellular environment, which we find to be many orders of magnitude larger than unity in natural units. From these calculations, we construct a phase diagram indicating where each strategy is most efficient. Our results suggest that intracellular information transfer may constitute a substantial energetic cost. This provides a new tool for understanding tradeoffs in cellular network function.

Functional Site-Directed Fluorometry in Native Cells to Study Skeletal Muscle Excitability.

Functional site-directed fluorometry has been the technique of choice to investigate the structure-function relationship of numerous membrane proteins, including voltage-gated ion channels. This approach has been used primarily in heterologous expression systems to simultaneously measure membrane currents, the electrical manifestation of the channels' activity, and fluorescence measurements, reporting local domain rearrangements. Functional site-directed fluorometry combines electrophysiology, molecular biology, chemistry, and fluorescence into a single wide-ranging technique that permits the study of real-time structural rearrangements and function through fluorescence and electrophysiology, respectively. Typically, this approach requires an engineered voltage-gated membrane channel that contains a cysteine that can be tested by a thiol-reactive fluorescent dye. Until recently, the thiol-reactive chemistry used for the site-directed fluorescent labeling of proteins was carried out exclusively in Xenopus oocytes and cell lines, restricting the scope of the approach to primary non-excitable cells. This report describes the applicability of functional site-directed fluorometry in adult skeletal muscle cells to study the early steps of excitation-contraction coupling, the process by which muscle fiber electrical depolarization is linked to the activation of muscle contraction. The present protocol describes the methodologies to design and transfect cysteine-engineered voltage-gated Ca2+ channels (CaV1.1) into muscle fibers of the flexor digitorum brevis of adult mice using in vivo electroporation and the subsequent steps required for functional site-directed fluorometry measurements. This approach can be adapted to study other ion channels and proteins. The use of functional site-directed fluorometry of mammalian muscle is particularly relevant to studying basic mechanisms of excitability.

Dependence of the Atrioventricular Conduction Time on the Conduction through the Atrioventricular Node and His-Purkinje System.

The electrical depolarization of the heart passes through various structures of the cardiac conduction system, which modify its conduction to different extents. In this study, we investigated the relationship between the atrioventricular conduction time (AV interval) and its contributors, the atrioventricular node (AVN) and the His-Purkinje system (HPS), as represented by the AH and HV intervals, respectively. We also compared sex differences in these intervals and their relations. Resting intracardiac tracings lasting 5 min were obtained from 64 patients (33 women) during an invasive electrophysiological study. The aforementioned intervals were measured for all consecutive beats. The mean AH interval was 85.9 ms, HV 43.7 ms, and AV 129.6 ms. Men had longer AH (80.0 vs. 65.9 ms), HV (38.4 vs. 35.3 ms), and AV intervals (124.7 vs. 108.5 ms) than women. The AV intervals were linearly correlated with AH intervals in all patients (r2 = 0.65). No significant correlation was found between AV and HV intervals in all patients (r2 = 0.05). There were no sex differences in these associations. Our results suggest that the atrioventricular conduction time depends mainly on the conduction through the AVN and less on the HPS. These relations are similar in both sexes, although men had longer conduction times through the AVN, HPS, and total atrioventricular conduction time.

Diminishing neuronal acidification by channelrhodopsins with low proton conduction

Many channelrhodopsins are permeable to protons. We show that in electrically polarized cells, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification. From an initial intracellular pH of 7.3, cells acidified to pH 6.9 ± 0.24 (mean ± s.d., n = 34 cells) after 60 seconds of illumination. To determine whether this acidification arose via proton transport through the opsin vs through other voltage-dependent proton channels, we performed experiments with patterned optogenetic stimulation in monolayers of HEK293 cells expressing CheRiff, an inward-rectifier potassium channel, Kir2.1, and a red-shifted pH indicator, pHoran4. Illumination with stripes of blue light led to electrical depolarization that extended beyond the illuminated spots, due to gap junctional conduction; but acidification was localized to the illuminated spots. These observations established that the acidification required proton transport through the opsin itself. We then identified and characterized two opsins which showed large photocurrents, but small proton permeability, PsCatCh2.0 and ChR2 3M. These opsins were effective at evoking neural activity, but neither induced detectable acidification. PsCatCh2.0 was also spectrally compatible with simultaneous voltage imaging with QuasAr6a. Stimulation-evoked acidification is a possible source of artifacts and disruptions to cell health in scientific and prospective therapeutic applications of optogenetics. Channelrhodopsins with low proton permeability are a promising strategy for avoiding these problems.

Nanomolar clodronate induces adenosine accumulation in the perfused rat mesenteric bed and mesentery-derived endothelial cells.

The vesicular nucleotide transporter (VNUT) is critical for sympathetic co-transmission and purinergic transmission maintenance. To examine this proposal, we assessed whether the bisphosphonate clodronate, claimed as a potent in vitro VNUT blocker, modified spontaneous and/or the electrically evoked overflow of ATP/metabolites and NA from mesentery sympathetic perivascular nerve terminals. Additionally, in primary endothelial cell cultures derived from this tissue, we also evaluated whether clodronate interfered with ATP/metabolite cell outflow and metabolism of N6-etheno adenosine 5'-triphosphate (eATP), N6-etheno adenosine (eADO), and adenosine deaminase enzyme activity. Rat mesenteries were perfused in the absence or presence of .01-1,000nM clodronate, 1-1,000nM Evans blue (EB), and 1-10µM DIDS; tissue perfusates were collected to determine ATP/metabolites and NA before, during, and after perivascular electrical nerve terminal depolarization. An amount of 1-1,000nM clodronate did not modify the time course of ATP or NA overflow elicited by nerve terminal depolarization, and only 10nM clodronate significantly augmented perfusate adenosine. Electrical nerve terminal stimulation increased tissue perfusion pressure that was significantly reduced only by 10nM clodronate [90.0 ± 18.6 (n = 8) to 35.0 ± 10.4 (n = 7), p = .0277]. As controls, EB, DIDS, or reserpine treatment reduced the overflow of ATP/metabolites and NA in a concentration-dependent manner elicited by nerve terminal depolarization. Moreover, mechanical stimulation of primary endothelial cell cultures from the rat mesentery added with 10 or 100nM clodronate increased adenosine in the cell media. eATP was metabolized by endothelial cells to the same extent with and without 1-1,000nM clodronate, suggesting the bisphosphonate did not interfere with nucleotide ectoenzyme metabolism. In contrast, extracellular eADO remained intact, indicating that this nucleoside is neither metabolized nor transported intracellularly. Furthermore, only 10nM clodronate inhibited (15.5%) adenosine metabolism to inosine in endothelial cells as well as in a commercial crude adenosine deaminase enzyme preparation (12.7%), and both effects proved the significance (p < .05). Altogether, present data allow inferring that clodronate inhibits adenosine deaminase activity in isolated endothelial cells as in a crude extract preparation, a finding that may account for adenosine accumulation following clodronate mesentery perfusion.

Applying the Inelastic Thermal Spike Model to the Investigation of Damage Induced by High‐Energy Ions in Polymers

AbstractThis work reports on damage production in polymers by high‐energy ions within the framework of the inelastic thermal spike model (i‐TS). The model is used to describe the effective size of the damaged region around the ion path (the track size) in amorphous poly(methyl methacrylate) (PMMA) and the semicrystalline poly(p‐phenylene sulphide) (PPS), poly(ethylene terephthalate) (PET), and poly(vinylidene difluoride) (PVDF). Track size calculations are compared to experimental data deduced from measurements of crater size, bond‐breaking cross‐sections, changes in crystallinity and electron density, track etching, and electrical depolarization. The use of data obtained from distinct types of damage provides a broad platform to test the applicability of the model to polymers. This work shows that the i‐TS correctly describes the dependence of the track size on energy loss obtained from most experimental probes, when the activation energy of thermal decomposition of the polymers is used as the criterion of track formation, using an electron–phonon mean free path of ≈3 nm. As damage is not uniform across the ion track radial dimension, there are fine variations in the experimental damage radii that can only be accounted for by using multiple activation processes. Amorphization radii of the semicrystalline polymers are not directly correlated to melting induced by the ions.

Vectocardiographic analysis of right ventricular electrical conduction delay

Introduction: The electrocardiographic interpretation of end conduction delay (ECD) in the right ventricular branch of the heart has already generated some hypotheses that this right branch is not single, as anatomically demonstrated, and can be divided into distinct terminal branches when we analyze tracings through the vectorcardiogram. Methods: There were 227 electrocardiograms selected, with typical characteristics defined as ECD of patients from the electrocardiography service of the Centro Universitário Saúde ABC, of both sexes, in the age range of 18 to 87 years, with varied ethnicities, weight and height, with cardiovascular risk factors or without them. We performed vectorcardiograms in these patients to observe the behavior of the final portion of electrical conduction. Results: Analyzing the vectorcardiographic tracings of patients who presented ECD in electrocardiogram, we confirmed in the recording by the frontal plane, the presence of ECD but recorded in three distinct regions; 103 patients in the right upper quadrant between -120° and -150°, 45 patients in the right lower quadrant between +170° and -170°, and medial, and 79 patients in the right lower quadrant between +110° and + 140°. Conclusion: Electrical depolarization of the heart in the right ventricle in electrocardiographic tracings apparently records typical alterations that we can diagnose as depolarization of a single bundle; but when we performed vectorcardiograms, we recorded three distinct zones of right ventricular depolarization with delay; i.e., three distinct sectors of right ventricle free wall delay, such as type I (upper), type II (lower) and type III (medial).

Depolarization and repolarization dynamics after His-bundle pacing: Comparison with right ventricular pacing and native ventricular conduction.

BackgroundThe current study aimed to evaluate changes in electrical depolarization and repolarization parameters after His‐bundle pacing (HBP) compared with right ventricular pacing (RVP) and its association with ventricular arrhythmia (VA).MethodsForty‐one patients (13 with HBP, 14 with RVP, and 14 controls [AAI mode]) were evaluated. After continuous pacing algorithm, QRS duration, QT interval, QTc, JT interval, T‐peak to T‐end (Tpe), and Tpe/QT ratio were measured on electrocardiography at baseline and 1 week, 1 month, and 6 months postoperatively. We investigated VA occurrence and adverse events after implantation.ResultsAt 6 months, QRS duration was significantly shorter in the HBP (121.6 ± 15.6 ms) than in the RVP (150.1 ± 14.9 ms) group. The QT intervals were lower in the HBP (424.0 ± 40.9 ms) and control (405.9 ± 23.0 ms) groups than in the RVP (453.0 ± 40.2 ms) group. The Tpe and Tpe/QT ratios at 6 months differed significantly between the HBP and RVP groups (Tpe, 69.8 ± 19.7 ms vs 87.4 ± 11.9 ms and Tpe/QT, 0.16 ± 0.03 vs 0.19 ± 0.02, respectively). The Tpe and Tpe/QT ratios were similarly shortened in the HBP and control groups. VA occurred less frequently in the HBP (15%) and control (7.1%) groups than in the RVP (50%) group (p = 0.020). The non‐RVP group showed significantly lower rates of VA and major adverse events than the RVP group. Patients with VA demonstrated significantly longer QRS duration, QT interval, Tpe, and Tpe/QT at 6 months than those without VA.ConclusionHBP showed better depolarization and repolarization stability than RVP.

Development and Application of Automatized Routines for Optical Analysis of Synaptic Activity Evoked by Chemical and Electrical Stimulation.

The recent development of cellular imaging techniques and the application of genetically encoded sensors of neuronal activity led to significant methodological progress in neurobiological studies. These methods often result in complex and large data sets consisting of image stacks or sets of multichannel fluorescent images. The detection of synapses, visualized by fluorescence labeling, is one major challenge in the analysis of these datasets, due to variations in synapse shape, size, and fluorescence intensity across the images. For their detection, most labs use manual or semi-manual techniques that are time-consuming and error-prone. We developed SynEdgeWs, a MATLAB-based segmentation algorithm that combines the application of an edge filter, morphological operators, and marker-controlled watershed segmentation. SynEdgeWs does not need training data and works with low user intervention. It was superior to methods based on cutoff thresholds and local maximum guided approaches in a realistic set of data. We implemented SynEdgeWs in two automatized routines that allow accurate, direct, and unbiased identification of fluorescently labeled synaptic puncta and their consecutive analysis. SynEval routine enables the analysis of three-channel images, and ImgSegRout routine processes image stacks. We tested the feasibility of ImgSegRout on a realistic live-cell imaging data set from experiments designed to monitor neurotransmitter release using synaptic phluorins. Finally, we applied SynEval to compare synaptic vesicle recycling evoked by electrical field stimulation and chemical depolarization in dissociated cortical cultures. Our data indicate that while the proportion of active synapses does not differ between stimulation modes, significantly more vesicles are mobilized upon chemical depolarization.

Evaluation of radiolabeled acetylcholine synthesis and release in rat striatum.

Cholinergic transmission underlies higher brain functions such as cognition and movement. To elucidate the process whereby acetylcholine (ACh) release is maintained and regulated in the central nervous system, uptake of [3 H]choline and subsequent synthesis and release of [3 H]ACh were investigated in rat striatal segments. Incubation with [3 H]choline elicited efficient uptake via high-affinity choline transporter-1, resulting in accumulation of [3 H]choline and [3 H]ACh. However, following inhibition of ACh esterase (AChE), incubation with [3 H]choline led predominantly to the accumulation of [3 H]ACh. Electrical stimulation and KCl depolarization selectively released [3 H]ACh but not [3 H]choline. [3 H]ACh release gradually declined upon repetitive stimulation, whereas the release was reproducible under inhibition of AChE. [3 H]ACh release was abolished after treatment with vesamicol, an inhibitor of vesicular ACh transporter. These results suggest that releasable ACh is continually replenished from the cytosol to releasable pools of cholinergic vesicles to maintain cholinergic transmission. [3 H]ACh release evoked by electrical stimulation was abolished by tetrodotoxin, but that induced by KCl was largely resistant. ACh release was Ca2+ dependent and exhibited slightly different sensitivities to N- and P-type Ca2+ channel toxins (ω-conotoxin GVIA and ω-agatoxin IVA, respectively) between both stimuli. [3 H]ACh release was negatively regulated by M2 muscarinic and D2 dopaminergic receptors. The present results suggest that inhibition of AChE within cholinergic neurons and of presynaptic negative regulation of ACh release contributes to maintenance and facilitation of cholinergic transmission, providing a potentially useful clue for the development of therapies for cholinergic dysfunction-associated disorders, in addition to inhibition of synaptic cleft AChE.

Engaging biological oscillators through second messenger pathways permits emergence of a robust gastric slow-wave during peristalsis

Peristalsis, the coordinated contraction—relaxation of the muscles of the stomach is important for normal gastric motility and is impaired in motility disorders. Coordinated electrical depolarizations that originate and propagate within a network of interconnected layers of interstitial cells of Cajal (ICC) and smooth muscle (SM) cells of the stomach wall as a slow-wave, underly peristalsis. Normally, the gastric slow-wave oscillates with a single period and uniform rostrocaudal lag, exhibiting network entrainment. Understanding of the integrative role of neurotransmission and intercellular coupling in the propagation of an entrained gastric slow-wave, important for understanding motility disorders, however, remains incomplete. Using a computational framework constituted of a novel gastric motility network (GMN) model we address the hypothesis that engaging biological oscillators (i.e., ICCs) by constitutive gap junction coupling mechanisms and enteric neural innervation activated signals can confer a robust entrained gastric slow-wave. We demonstrate that while a decreasing enteric neural innervation gradient that modulates the intracellular IP3 concentration in the ICCs can guide the aboral slow-wave propagation essential for peristalsis, engaging ICCs by recruiting the exchange of second messengers (inositol trisphosphate (IP3) and Ca2+) ensures a robust entrained longitudinal slow-wave, even in the presence of biological variability in electrical coupling strengths. Our GMN with the distinct intercellular coupling in conjunction with the intracellular feedback pathways and a rostrocaudal enteric neural innervation gradient allows gastric slow waves to oscillate with a moderate range of frequencies and to propagate with a broad range of velocities, thus preventing decoupling observed in motility disorders. Overall, the findings provide a mechanistic explanation for the emergence of decoupled slow waves associated with motility impairments of the stomach, offer directions for future experiments and theoretical work, and can potentially aid in the design of new interventional pharmacological and neuromodulation device treatments for addressing gastric motility disorders.

Study on dynamic properties of 1–3 cement-based piezoelectric composites

In this paper, Hopkinson compression bar technology is used to test the related properties of 1–3 cement-based piezoelectric composites under dynamic load. The research results prove that the stress and electric displacement of 1–3 cement-based piezoelectric composites have similar changing trends under dynamic action, that is, the response state of mechanical and electrical properties of the specimens is good. At the same time, due to the action of force, the phenomenon of electrical domain deflection and depolarization occurs, and the piezoelectric properties of the material also weaken with the increase of the number of loading.

Pulse arrival time as a surrogate of blood pressure

Various models have been proposed for the estimation of blood pressure (BP) from pulse transit time (PTT). PTT is defined as the time delay of the pressure wave, produced by left ventricular contraction, measured between a proximal and a distal site along the arterial tree. Most researchers, when they measure the time difference between the peak of the R-wave in the electrocardiogram signal (corresponding to left ventricular depolarisation) and a fiducial point in the photoplethysmogram waveform (as measured by a pulse oximeter attached to the fingertip), describe this erroneously as the PTT. In fact, this is the pulse arrival time (PAT), which includes not only PTT, but also the time delay between the electrical depolarisation of the heart’s left ventricle and the opening of the aortic valve, known as pre-ejection period (PEP). PEP has been suggested to present a significant limitation to BP estimation using PAT. This work investigates the impact of PEP on PAT, leading to a discussion on the best models for BP estimation using PAT or PTT. We conducted a clinical study involving 30 healthy volunteers (53.3% female, 30.9 ± 9.35 years old, with a body mass index of 22.7 ± 3.2 kg/m^{2}). Each session lasted on average 27.9 ± 0.6 min and BP was varied by an infusion of phenylephrine (a medication that causes venous and arterial vasoconstriction). We introduced new processing steps for the analysis of PAT and PEP signals. Various population-based models (Poon, Gesche and Fung) and a posteriori models (inverse linear, inverse squared and logarithm) for estimation of BP from PTT or PAT were evaluated. Across the cohort, PEP was found to increase by 5.5 ms ± 4.5 ms from its baseline value. Variations in PTT were significantly larger in amplitude, − 16.8 ms ± 7.5 ms. We suggest, therefore, that for infusions of phenylephrine, the contribution of PEP on PAT can be neglected. All population-based models produced large BP estimation errors, suggesting that they are insufficient for modelling the complex pathways relating changes in PTT or PAT to changes in BP. Although PAT is inversely correlated with systolic blood pressure (SBP), the gradient of this relationship varies significantly from individual to individual, from − 2946 to − 470.64 mmHg/s in our dataset. For the a posteriori inverse squared model, the root mean squared errors (RMSE) for systolic and diastolic blood pressure (DBP) estimation from PAT were 5.49 mmHg and 3.82 mmHg, respectively. The RMSEs for SBP and DBP estimation by PTT were 4.51 mmHg and 3.53 mmHg, respectively. These models take into account individual calibration curves required for accurate blood pressure estimation. The best performing population-based model (Poon) reported error values around double that of the a posteriori inverse squared model, and so the use of population-based models is not justified.

Spatial Feature Extraction of Vectorcardiography via Minimum Volume Ellipsoid Enclosure in Classifying Left Ventricular Hypertrophy.

The voltage criteria used to diagnose left ventricular hypertrophy (LVH) in the chest and limb leads are by no means absolute. In addition to QRS voltages, QRS axis and duration, and P wave characteristics, repolarization (STT) changes have been focused attention due to their representing left ventricular overload. Vectorcardiography (VCG) has been studied specifically on its repolarization abnormality. The present study aims to devise spatial feature extraction of VCG and assess it in the LVH classification task. A minimum volume ellipsoid enclosure was applied to six segments obtained from upstroke and downstroke of each P, QRS, and T loops of a single-beat VCG. For the evaluation, VCG and 12 lead ECG dataset along with LVH labels of 61 subjects were derived from public open data, PTB-XL. These classification performances were compared with the LVH diagnosis criteria in the standard 12 lead ECG. As a result, the Random Forest classifier trained by the proposed spatial VCG feature resulted in accuracy of 0.904 (95% confidence interval: 0.861-0.947) when the classbalanced dataset was evaluated, which slightly exceeded the feature of 12 lead ECG. The feature importance analysis provided the quantitative ranking of the spatial feature of VCG, which were practically similar to those of ECG in the LVH classification task. Since the VCG are spatially comparable with three-dimensional data of CT, MRI, or Echocardiography, VCG will shed light on the spatial behavior of electrical depolarization and repolarization abnormalities in cardiac diseases.

Non-conserved residues dictate dopamine transporter selectivity for the potent synthetic cathinone and psychostimulant MDPV

Clandestine chemists are currently exploiting the pyrrolidinophenone scaffold to develop new designer drugs that carry the risk of abuse and overdose. These drugs promote addiction through the rewarding effects of increased dopaminergic neurotransmission. 3,4-Methylenedioxypyrovalerone (MDPV) and its analogs are illicit psychostimulants of this class that are ∼50-fold more potent than cocaine at inhibiting the human dopamine transporter (hDAT). In contrast, MDPV is a weak inhibitor at both the human serotonin transporter (hSERT) and, as it is shown here, the Drosophila melanogaster DAT (dDAT). We studied three conserved residues between hSERT and dDAT that are unique in hDAT (A117, F318, and P323 in dDAT), and one residue that is different in all three transporters (D121 in dDAT). hDAT residues were replaced in the dDAT sequence at these positions using site-directed mutagenesis and stable cell lines were generated expressing these mutant transporters. The potencies of MDPV and two of its analogs were determined using a Ca2+-mobilization assay. In this assay, voltage-gated Ca2+ channels are expressed to sense the membrane electrical depolarization evoked when dopamine is transported through DAT. Each individual mutant slightly improved MDPV's potency, but the combination of all four increased its potency ∼100-fold (2 log units) in inhibiting dDAT activity. Molecular modeling and docking studies were conducted to explore the possible mode of interaction between MDPV and DAT in silico. Two of the studied residues (F318 and P323) are at the entrance of the S1 binding site, whereas the other two (A117 and D121) face the aryl moiety of MDPV when bound to this site. Therefore, these four non-conserved residues can influence MDPV selectivity not only by stabilizing binding, but also by controlling access to its binding site at DAT.

Electrical transport in lead-free Na0.5Bi0.5TiO3 ceramics

Lead-free Na0.5Bi0.5TiO3 (NBT) ceramics were prepared via a conventional oxide-mixed sintering route and their electrical transport properties were investigated. Direct current (DC, σDC) and alternating current (AC, σAC) electrical conductivity values, polarization current (first measurements) and depolarization current, current–voltage (I–U) characteristics (first measurements), and the Seebeck coefficient (α) were determined under various conditions. The mechanism of depolarization and the electrical conductivity phenomena observed for the investigated samples were found to be typical. For low voltages, the I–U characteristics were in good agreement with Ohm’s law; for higher voltages, the observed dependences were I–U2, I–U4, and then I–U6. The low-frequency σAC followed the formula σAC–ωs (ω is the angular frequency and s is the frequency exponent). The exponent s was equal to 0.18–0.77 and 0.73–0.99 in the low- and high-frequency regions, respectively, and decreased with temperature increasing. It was shown that conduction mechanisms involved the hopping of charge carriers at low temperatures, small polarons at intermediate temperatures, and oxygen vacancies at high temperatures. Based on AC conductivity data, the density of states at the Fermi-level, and the minimum hopping length were estimated. Electrical conduction was found to undergo p–n–p transitions with increasing temperature. These transitions occurred at depolarization temperature Td, 280 ℃, and temperature of the maximum of electric permittivity Tm is as typical of NBT materials.

Identification of single motor units in skeletal muscle under low force isometric voluntary contractions using ultrafast ultrasound

The central nervous system (CNS) controls skeletal muscles by the recruitment of motor units (MUs). Understanding MU function is critical in the diagnosis of neuromuscular diseases, exercise physiology and sports, and rehabilitation medicine. Recording and analyzing the MUs’ electrical depolarization is the basis for state-of-the-art methods. Ultrafast ultrasound is a method that has the potential to study MUs because of the electrical depolarizations and consequent mechanical twitches. In this study, we evaluate if single MUs and their mechanical twitches can be identified using ultrafast ultrasound imaging of voluntary contractions. We compared decomposed spatio-temporal components of ultrasound image sequences against the gold standard needle electromyography. We found that 31% of the MUs could be successfully located and their firing pattern extracted. This method allows new non-invasive opportunities to study mechanical properties of MUs and the CNS control in neuromuscular physiology.

Influence of MoO3 on electrical properties and thermal depolarization of Bi0.5Na0.5TiO3-BaTiO3 lead-free piezoceramics

In this work, electric properties of undoped and MoO3-doped 0.93Bi0.5Na0.5TiO3-0.07BaTiO3 ceramics (BNT-BT: x mol. % MoO3) are systematically studied. At room temperature, the optimum piezoelectric property (d33 = 177.0 pC/N) was observed in BNT-BT: 0.10Mo ceramics, with remanent polarization (Pr = 32.15 μC/cm2), electromechanical coupling coefficient (kt = 0.578, kp = 0.169, k31 = 0.180), and mechanical quality factor (Qm = 90.3). Mo doping was found to have a positive effect on the depolarization temperature Td, and k31 showed excellent thermal stability at BNT-BT: 0.05Mo ceramics. These findings confirm that Mo doping is an effective method to improve BNT-based lead-free ceramics.