RESUMO

High-voltage power line insulators are crucial for safe and efficient electricity transmission. However, real-world image limitations, particularly regarding dirty insulator strings, delay the development of robust algorithms for insulator inspection. This dataset addresses this challenge by creating a novel synthetic high-voltage power line insulator image database. The database was created using computer-aided design softwares and a game development engine. Publicly available CAD models of high-voltage towers with the most common insulator types (polymer, glass, and porcelain) were imported into the game engine. This virtual environment allowed for the generation of a diverse dataset by manipulating virtual cameras, simulating various lighting conditions, and incorporating different backgrounds such as mountains, forests, plantation, rivers, city and deserts. The database comprises two main sets: The Image Segmentation Set, which includes 47,286 images categorized by insulator material (ceramic, polymeric, and glass) and landscape type (mountains, forests, plantation, rivers, city and deserts). Moreover, the Image Classification Set that contains 14,424 images simulating common insulator string contaminants: salt, soot, bird excrement, and clean insulators. Each contaminant category has 3,606 images divided into 1,202 images per insulator type. This synthetic database offers a valuable resource for training and evaluating machine learning algorithms for high-voltage power line insulator inspection, ultimately contributing to enhanced power grid maintenance and reliability.

RESUMO

The development of cell-based fluorescent assays has resulted in an incredible tool for searching new ion channels' modulators with a biophysical and clinical profile. Among all the ion channels, potassium (K+)-permeable channels represent the most diverse and relevant for cell function, making them attractive targets for drug discovery. Some of the cell-based assays for K+ channels take advantage of a thallium-sensitive dye whose fluorescence increased upon the binding of thallium (Tl+), an ion able to move through K+ channels. We optimize the FLIPR Potassium Assay Kit based on thallium influx to measure the Kv10.1 activity.

Assuntos

Tálio , Tálio/metabolismo , Humanos , Corantes Fluorescentes/química , Células HEK293 , Fluorescência , Canais de Potássio Éter-A-Go-Go

RESUMO

Studies on the interaction sites of peptide toxins and ion channels typically involve site-directed mutations in toxins. However, natural mutant toxins exist among them, offering insights into how the evolutionary process has conserved crucial sequences for activities and molecular target selection. In this study, we present a comparative investigation using electrophysiological approaches and computational analysis between two alpha toxins from evolutionarily close scorpion species of the genus Tityus, namely, Tst3 and Ts3 from T. stigmurus and T. serrulatus, respectively. These toxins exhibit three natural substitutions near the C-terminal region, which is directly involved in the interaction between alpha toxins and Nav channels. Additionally, we characterized the activity of the Tst3 toxin on Nav1.1-Nav1.7 channels. The three natural changes between the toxins did not alter sensitivity to Nav1.4, maintaining similar intensities regarding their ability to alter opening probabilities, delay fast inactivation, and induce persistent currents. Computational analysis demonstrated a preference for the down conformation of VSD4 and a shift in the conformational equilibrium towards this state. This illustrates that the sequence of these toxins retained the necessary information, even with alterations in the interaction site region. Through electrophysiological and computational analyses, screening of the Tst3 toxin on sodium isoform revealed its classification as a classic α-NaTx with a broad spectrum of activity. It effectively delays fast inactivation across all tested isoforms. Structural analysis of molecular energetics at the interface of the VSD4-Tst3 complex further confirmed this effect.

Assuntos

Venenos de Escorpião , Escorpiões , Venenos de Escorpião/química , Venenos de Escorpião/genética , Animais , Brasil , Humanos , Xenopus laevis , Ativação do Canal Iônico/efeitos dos fármacos , Sequência de Aminoácidos , Animais Peçonhentos

RESUMO

The Cupressaceae family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like Chamaecyparis lawsoniana (C. lawsoniana) are commonly found in urban areas. We investigated whether C. lawsoniana exerts some of its effects by modifying airway smooth muscle (ASM) contractility. The leaves of C. lawsoniana (363 g) were pulverized mechanically, and extracts were obtained by successive maceration 1:10 (w:w) with methanol/CHCl3. Guinea pig tracheal rings were contracted with KCl, tetraethylammonium (TEA), histamine (HIS), or carbachol (Cch) in organ baths. In the Cch experiments, tissues were pre-incubated with D-600, an antagonist of L-type voltage-dependent Ca2+ channels (L-VDCC) before the addition of C. lawsoniana. Interestingly, at different concentrations, C. lawsoniana diminished the tracheal contractions induced by KCl, TEA, HIS, and Cch. In ASM cells, C. lawsoniana significantly diminished L-type Ca2+ currents. ASM cells stimulated with Cch produced a transient Ca2+ peak followed by a sustained plateau maintained by L-VDCC and store-operated Ca2+ channels (SOCC). C. lawsoniana almost abolished this last response. These results show that C. lawsoniana, and its active metabolite quercetin, relax the ASM by inhibiting the L-VDCC and SOCC; further studies must be performed to obtain the complete set of metabolites of the extract and study at length their pharmacological properties.

Assuntos

Cálcio , Chamaecyparis , Contração Muscular , Músculo Liso , Extratos Vegetais , Quercetina , Traqueia , Animais , Cobaias , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Contração Muscular/efeitos dos fármacos , Quercetina/farmacologia , Quercetina/química , Traqueia/efeitos dos fármacos , Traqueia/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Chamaecyparis/química , Cálcio/metabolismo , Masculino , Bloqueadores dos Canais de Cálcio/farmacologia , Histamina/metabolismo , Canais de Cálcio Tipo L/metabolismo , Folhas de Planta/química

RESUMO

Metabolic changes are critical in the regulation of Ca2+ influx in central and peripheral neuroendocrine cells. To study the regulation of L-type Ca2+ channels by AMPK we used biochemical reagents and ATP/glucose-concentration manipulations in rat chromaffin cells. AICAR and Compound-C, at low concentration, significantly induce changes in L-type Ca2+ channel-current amplitude and voltage dependence. Remarkably, an overlasting decrease in the channel-current density can be induced by lowering the intracellular level of ATP. Accordingly, Ca2+ channel-current density gradually diminishes by decreasing the extracellular glucose concentration. By using immunofluorescence, a decrease in the expression of CaV1.2 is observed while decreasing extracellular glucose, suggesting that AMPK reduces the number of functional Ca2+ channels into the plasma membrane. Together, these results support for the first time the dependence of metabolic changes in the maintenance of Ca2+ channel-current by AMPK. They reveal a key step in Ca2+ influx in secretory cells.

Assuntos

Proteínas Quinases Ativadas por AMP , Aminoimidazol Carboxamida , Canais de Cálcio Tipo L , Células Cromafins , Glucose , Animais , Células Cromafins/metabolismo , Células Cromafins/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Ratos , Glucose/metabolismo , Glucose/farmacologia , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Trifosfato de Adenosina/metabolismo , Ribonucleotídeos/farmacologia , Pirimidinas/farmacologia , Cálcio/metabolismo , Pirazóis/farmacologia , Células Cultivadas , Ratos Wistar , Ativação do Canal Iônico/efeitos dos fármacos

RESUMO

L-type calcium channels are essential for the excitation-contraction coupling in cardiac muscle. The CaV1.2 channel is the most predominant isoform in the ventricle which consists of a multi-subunit membrane complex that includes the CaV1.2 pore-forming subunit and auxiliary subunits like CaVα2δ and CaVß2b. The CaV1.2 channel's C-terminus undergoes proteolytic cleavage, and the distal C-terminal domain (DCtermD) associates with the channel core through two domains known as proximal and distal C-terminal regulatory domain (PCRD and DCRD, respectively). The interaction between the DCtermD and the remaining C-terminus reduces the channel activity and modifies voltage- and calcium-dependent inactivation mechanisms, leading to an autoinhibitory effect. In this study, we investigate how the interaction between DCRD and PCRD affects the inactivation processes and CaV1.2 activity. We expressed a 14-amino acid peptide miming the DCRD-PCRD interaction sequence in both heterologous systems and cardiomyocytes. Our results show that overexpression of this small peptide can displace the DCtermD and replicate the effects of the entire DCtermD on voltage-dependent inactivation and channel inhibition. However, the effect on calcium-dependent inactivation requires the full DCtermD and is prevented by overexpression of calmodulin. In conclusion, our results suggest that the interaction between DCRD and PCRD is sufficient to bring about the current inhibition and alter the voltage-dependent inactivation, possibly in an allosteric manner. Additionally, our data suggest that the DCtermD competitively modifies the calcium-dependent mechanism. The identified peptide sequence provides a valuable tool for further dissecting the molecular mechanisms that regulate L-type calcium channels' basal activity in cardiomyocytes.

Assuntos

Canais de Cálcio Tipo L , Miócitos Cardíacos , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo L/química , Animais , Miócitos Cardíacos/metabolismo , Humanos , Células HEK293 , Ratos , Domínios Proteicos

RESUMO

BACKGROUND: The efficacy and safety of adjunctive low-voltage area (LVA) ablation on outcomes of catheter ablation (CA) for atrial fibrillation (AF) remains uncertain. METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) comparing CA with versus without LVA ablation for patients with AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. Our primary endpoint was recurrence of atrial tachyarrhythmia (ATA), including AF, atrial flutter, or atrial tachycardia. We used R version 4.3.1 for all statistical analyses. RESULTS: Our meta-analysis included 10 RCTs encompassing 1780 patients, of whom 890 (50%) were randomized to LVA ablation. Adjunctive LVA ablation significantly reduced recurrence of ATA (RR 0.76; 95% CI 0.67-0.88; p < .01) and reduced the number of redo ablation procedures (RR 0.54; 95% CI 0.35-0.85; p < .01), as compared with conventional ablation. Among 691 (43%) patients with documented LVAs on baseline substrate mapping, adjunctive LVA ablation substantially reduced ATA recurrences (RR 0.57; 95% CI 0.38-0.86; p < .01). There was no significant difference between groups in terms of periprocedural adverse events (RR 0.78; 95% CI 0.39-1.56; p = .49). CONCLUSIONS: Adjunctive LVA ablation is an effective and safe strategy for reducing recurrences of ATA among patients who undergo CA for AF.

Assuntos

Potenciais de Ação , Fibrilação Atrial , Ablação por Cateter , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Ablação por Cateter/efeitos adversos , Resultado do Tratamento , Masculino , Fatores de Risco , Feminino , Pessoa de Meia-Idade , Frequência Cardíaca , Idoso , Fatores de Tempo

Assuntos

Canal de Sódio Disparado por Voltagem NAV1.7 , Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Humanos , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Bloqueadores dos Canais de Sódio/farmacologia , Bloqueadores dos Canais de Sódio/uso terapêutico , Masculino , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêutico

RESUMO

Piezoelectric cement-based composites could serve to monitor the strain state of structural elements or act as self-powered materials in structural health monitoring (SHM) applications. The incorporation of piezoelectric materials as an active phase within cement matrices has presented a highly attractive avenue until today. However, their application is challenged by the low electrical conductivity of the hydrated cement matrix. Gold nanoparticles (Au NPs) possess substantial potential for elevating the free electrical charge within the matrix, increasing its electrical conductivity between the Au NPs and the cement matrix, thereby enhancing the piezoelectric response of the composite. In this sense, the objective of this study is to investigate the effects of incorporating low concentrations of gold nanoparticles (Au NPs) (442 and 658 ppm) on the electrical and piezoelectric properties of cement-based composites. Additionally, this study considers the effects of such properties when the material is cured under a constant electric field. Electrical impedance spectroscopy was used to evaluate the polarization resistance and piezoresistive properties of the material. Additionally, open-circuit potential measurements were taken alongside the application of mechanical loads to assess the piezoelectric activity of the composites. The findings revealed a notable decrease in the composite's total electrical resistance, reaching a value of 1.5 ± 0.2 kΩ, almost four times lower than the reference specimens. In the realm of piezoelectricity, the piezoelectric voltage parameter g33 exhibited a remarkable advancement, improving by a factor of 57 when compared to reference specimens. This significant enhancement can be attributed to both the concentration of Au NPs and the electrical curing process. In summary, the outcomes of this study underscore the feasibility of creating a highly electrically conductive cement-based matrix, using low concentrations of gold nanoparticles as electric charge carries, and indicate the possible piezoelectric behavior of the studied compposite.

RESUMO

The eukaryotic cell is highly compartmentalized with organelles. Owing to their function in transporting metabolites, metabolic intermediates and byproducts of metabolic activity, organelles are important players in the orchestration of cellular function. Recent advances in optical methods for interrogating the different aspects of organellar activity promise to revolutionize our ability to dissect cellular processes with unprecedented detail. The transport activity of organelles is usually coupled to the transport of charged species; therefore, it is not only associated with the metabolic landscape but also entangled with membrane potentials. In this context, the targeted expression of fluorescent probes for interrogating organellar membrane potential (Ψorg) emerges as a powerful approach, offering less-invasive conditions and technical simplicity to interrogate cellular signalling and metabolism. Different research groups have made remarkable progress in adapting a variety of optical methods for measuring and monitoring Ψorg. These approaches include using potentiometric dyes, genetically encoded voltage indicators, hybrid fluorescence resonance energy transfer sensors and photoinduced electron transfer systems. These studies have provided consistent values for the resting potential of single-membrane organelles, such as lysosomes, the Golgi and the endoplasmic reticulum. We can foresee the use of dynamic measurements of Ψorg to study fundamental problems in organellar physiology that are linked to serious cellular disorders. Here, we present an overview of the available techniques, a survey of the resting membrane potential of internal membranes and, finally, an open-source mathematical model useful to interpret and interrogate membrane-bound structures of small volume by using the lysosome as an example.

Assuntos

Lisossomos , Organelas , Potenciais da Membrana , Organelas/metabolismo , Lisossomos/metabolismo , Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/análise , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo

RESUMO

Saxitoxin (STX) represents a marine toxin of significant concern due to its deleterious implications for aquatic ecosystems and public food safety. As a potent paralytic agent, the role of STX in obstructing voltage-gated sodium channels (VGSCs) is well-characterized. Yet, the mechanistic details underlying its low-dose toxicity remain largely enigmatic. In the current study, zebrafish embryos and larvae were subjected to subchronic exposure of graded STX concentrations (0, 1, 10, and 100 µg/L) until the 7th day post-fertilization. A tactile stimulus-based assay was employed to evaluate potential behavioral perturbations resulting from STX exposure. Both behavioral and transcription level analyses unveiled a compromised tactile response, which was found to be associated with a notable upregulation in the mRNA of two distinct VGSC isoforms, specifically the scn8aa/ab and scn1Laa/ab transcripts, even at the minimal STX dose. Notably, exposure to this lowest STX concentration also resulted in alterations in the transcriptional patterns of pivotal genes for cholinergic and GABAergic pathways, including ache and gabra1. Furthermore, STX induced a marked decrease in the levels of the neurotransmitter GABA. Our findings underscore that prolonged low-dose STX exposure during early development can significantly compromise the tactile response behavior in zebrafish. This study reveals that chronic low-dose STX exposure of developing zebrafish alters neurotransmission pathways that converge on altered tactile behavior.

RESUMO

Five peptides were isolated from the venom of the Mexican scorpion Centruroides bonito by chromatographic procedures (molecular weight sieving, ion exchange columns, and HPLC) and were denoted Cbo1 to Cbo5. The first four peptides contain 66 amino acid residues and the last one contains 65 amino acids, stabilized by four disulfide bonds, with a molecular weight spanning from about 7.5 to 7.8 kDa. Four of them are toxic to mice, and their function on human Na+ channels expressed in HEK and CHO cells was verified. One of them (Cbo5) did not show any physiological effects. The ones toxic to mice showed that they are modifiers of the gating mechanism of the channels and belong to the beta type scorpion toxin (ß-ScTx), affecting mainly the Nav1.6 channels. A phylogenetic tree analysis of their sequences confirmed the high degree of amino acid similarities with other known bona fide ß-ScTx. The envenomation caused by this venom in mice is treated by using commercially horse antivenom available in Mexico. The potential neutralization of the toxic components was evaluated by means of surface plasmon resonance using four antibody fragments (10FG2, HV, LR, and 11F) which have been developed by our group. These antitoxins are antibody fragments of single-chain antibody type, expressed in E. coli and capable of recognizing Cbo1 to Cbo4 toxins to various degrees.

Assuntos

Animais Peçonhentos , Perciformes , Peçonhas , Humanos , Cricetinae , Animais , Cavalos , Camundongos , Escorpiões , Cricetulus , Escherichia coli , Filogenia , Antivenenos , Aminoácidos , Fragmentos de Imunoglobulinas , Peptídeos

RESUMO

Cisplatin is a platinum-based chemotherapy drug widely used to treat various solid tumours. Although it is effective in anti-cancer therapy, many patients develop peripheral neuropathy during and after cisplatin treatment. Peripheral neuropathy results from lesions or diseases in the peripheral somatosensory nervous system and is a significant cause of debilitation and suffering in patients. In recent years, preclinical studies have been conducted to elucidate the mechanisms involved in chemotherapy-induced peripheral neuropathic pain, as well as to promote new therapeutic targets since current treatments are ineffective and are associated with adverse effects. G-protein coupled receptors and ion channels play a significant role in pain processing and may represent promising targets for improving the management of cisplatin-induced neuropathic pain. This review describes the role of G protein-coupled receptors and ion channels in cisplatin-induced pain, analysing preclinical experimental studies that investigated the role of each receptor subtype in the modulation of cisplatin-induced pain.

RESUMO

This study aimed to evaluate the influence of medium voltage electrical stimulation (ES) at three different intensities, 200 V (Treatment 200 V, T200), 300 V (Treatment 200 V, T300), and 400 V (Treatment 400 V, T400) on the initial pH decline in post mortem muscle and the quality parameters on M. longissimus thoracis - Nellore beef, both throughout the ageing process and during frozen storage. The colour, cooking loss, and shear force parameters for samples of aged beef were determined. Additional parameters, like thaw loss, pH, and lipid oxidation were also analyzed for the frozen storage. The shear force and cooking loss decreased and colour parameters increased in Nellore beef ES compared with CON on ageing time (14 days). At frozen storage, quality parameters like pH, a*, and b* were reduced over time, and no negative effect on lipid oxidation was found. Electrical stimulation at 200 V demonstrated effectiveness for decreasing shear force to Nellore beef (M. longissimus thoracis) during frozen storage. The application of medium voltage electrical stimulation can contribute to improved quality and tenderness in Nellore beef, both during ageing and frozen storage conditions.

Assuntos

Carne , Músculo Esquelético , Animais , Bovinos , Carne/análise , Músculo Esquelético/fisiologia , Estimulação Elétrica , Concentração de Íons de Hidrogênio , Lipídeos

RESUMO

The use of advanced modulation and control schemes for power converters, such as a Feedback Quantizer and Predictive Control, is widely studied in the literature. This work focuses on improving the closed-loop modulation scheme called Feedback Quantizer, which is applied to a three-phase voltage source inverter. This scheme has the natural behavior of mitigating harmonics at low frequencies, which are detrimental to electrical equipment such as transformers. This modulation scheme also provides good tracking for the voltage reference at the fundamental frequency. On the other hand, the disadvantage of this scheme is that it has a variable switching frequency, creating a harmonic spectrum in frequency dispersion, and it also needs a small sampling time to obtain good results. The proposed scheme to improve the modulation scheme is based on a Discrete Space Vector with virtual vectors to obtain a better approximation of the optimal vectors for use in the algorithm. The proposal improves the conventional scheme at a high sampling time (200 µs), obtaining a THD less than 2% in the load current, decreases the noise created by the conventional scheme, and provides a fixed switching frequency. Experimental tests demonstrate the correct operation of the proposed scheme.

RESUMO

The voltage-sensing domain (VSD) is a module capable of responding to changes in the membrane potential through conformational changes and facilitating electromechanical coupling to open a pore gate, activate proton permeation pathways, or promote enzymatic activity in some membrane-anchored phosphatases. To carry out these functions, this module acts cooperatively through conformational changes. The VSD is formed by four transmembrane segments (S1-S4) but the S4 segment is critical since it carries positively charged residues, mainly Arg or Lys, which require an aqueous environment for its proper function. The discovery of this module in voltage-gated ion channels (VGICs), proton channels (Hv1), and voltage sensor-containing phosphatases (VSPs) has expanded our understanding of the principle of modularity in the voltage-sensing mechanism of these proteins. Here, by sequence comparison and the evaluation of the relationship between sequence composition, intrinsic flexibility, and structural analysis in 14 selected representatives of these three major protein groups, we report five interesting differences in the folding patterns of the VSD both in prokaryotes and eukaryotes. Our main findings indicate that this module is highly conserved throughout the evolutionary scale, however: (1) segments S1 to S3 in eukaryotes are significantly more hydrophobic than those present in prokaryotes; (2) the S4 segment has retained its hydrophilic character; (3) in eukaryotes the extramembranous linkers are significantly larger and more flexible in comparison with those present in prokaryotes; (4) the sensors present in the kHv1 proton channel and the ciVSP phosphatase, both of eukaryotic origin, exhibit relationships of flexibility and folding patterns very close to the typical ones found in prokaryotic voltage sensors; and (5) archaeal channels KvAP and MVP have flexibility profiles which are clearly contrasting in the S3-S4 region, which could explain their divergent activation mechanisms. Finally, to elucidate the obscure origins of this module, we show further evidence for a possible connection between voltage sensors and TolQ proteins.

Assuntos

Ativação do Canal Iônico , Prótons , Ativação do Canal Iônico/fisiologia , Monoéster Fosfórico Hidrolases/genética

RESUMO

Voltage-gated proton channels (Hv1) are important regulators of the immunosuppressive function of myeloid-derived suppressor cells (MDSCs) in mice and have been proposed as a potential therapeutic target to alleviate dysregulated immunosuppression in tumors. However, till date, there is a lack of evidence regarding the functioning of the Hvcn1 and reports on mHv1 isoform diversity in mice and MDSCs. A computational prediction has suggested that the Hvcn1 gene may express up to six transcript variants, three of which are translated into distinct N-terminal isoforms of mHv1: mHv1.1 (269 aa), mHv1.2 (269 + 42 aa), and mHv1.3 (269 + 4 aa). To validate this prediction, we used RT-PCR on total RNA extracted from MDSCs, and the presence of all six predicted mRNA variances was confirmed. Subsequently, the open-reading frames (ORFs) encoding for mHv1 isoforms were cloned and expressed in Xenopus laevis oocytes for proton current recording using a macro-patch voltage clamp. Our findings reveal that all three isoforms are mammalian mHv1 channels, with distinct differences in their activation properties. Specifically, the longest isoform, mHv1.2, displays a right-shifted conductance-voltage (GV) curve and slower opening kinetics, compared to the mid-length isoform, mHv1.3, and the shortest canonical isoform, mHv1.1. While mHv1.3 exhibits a V0.5 similar to that of mHv1.1, mHv1.3 demonstrates significantly slower activation kinetics than mHv1.1. These results suggest that isoform gating efficiency is inversely related to the length of the N-terminal end. To further explore this, we created the truncated mHv1.2 ΔN20 construct by removing the first 20 amino acids from the N-terminus of mHv1.2. This construct displayed intermediate activation properties, with a V0.5 value lying intermediate of mHv1.1 and mHv1.2, and activation kinetics that were faster than that of mHv1.2 but slower than that of mHv1.1. Overall, these findings indicate that alternative splicing of the N-terminal exon in mRNA transcripts encoding mHv1 isoforms is a regulatory mechanism for mHv1 function within MDSCs. While MDSCs have the capability to translate multiple Hv1 isoforms with varying gating properties, the Hvcn1 gene promotes the dominant expression of mHv1.1, which exhibits the most efficient gating among all mHv1 isoforms.

RESUMO

The membrane potential of a cell (Vm) regulates several physiological processes. The voltage sensor domain (VSD) is a region that confers voltage sensitivity to different types of transmembrane proteins such as the following: voltage-gated ion channels, the voltage-sensing phosphatase (Ci-VSP), and the sperm-specific Na+/H+ exchanger (sNHE). VSDs contain four transmembrane segments (S1-S4) and several positively charged amino acids in S4, which are essential for the voltage sensitivity of the protein. Generally, in response to changes of the Vm, the positive residues of S4 displace along the plasma membrane without generating ionic currents through this domain. However, some native (e.g., Hv1 channel) and mutants of VSDs produce ionic currents. These gating pore currents are usually observed in VSDs that lack one or more of the conserved positively charged amino acids in S4. The gating pore currents can also be induced by the isolation of a VSD from the rest of the protein domains. In this review, we summarize gating pore currents from all families of proteins with VSDs with classification into three cases: (1) pathological, (2) physiological, and (3) artificial currents. We reinforce the model in which the position of S4 that lacks the positively charged amino acid determines the voltage dependency of the gating pore current of all VSDs independent of protein families.

Assuntos

Ativação do Canal Iônico , Sêmen , Masculino , Humanos , Ativação do Canal Iônico/fisiologia , Domínios Proteicos , Potenciais da Membrana , Aminoácidos

RESUMO

Microgrids represent a promising energy technology, because of the inclusion in them of clean and smart energy technologies. They also represent research challenges, including controllability, stability, and implementation. This article presents a dSPACE-control-platform-based implementation of a fixed-switching-frequency modulated model predictive control (M2PC) strategy, as an inner controller of a two-level, three-phase voltage source inverter (VSI) working in an islanded AC microgrid. The developed controller is hierarchical, as it includes a primary controller to share the load equally with the other power converter with its own local modulated predictive-based controller. All details of the implementation are given for establishing the dSPACE-based implementation of the control on a dSPACE ds1103 control platform, using MATLAB/Simulink for the controller design, I/O implementation and configuration with the embedded dSPACE's real-time interface in Simulink, and then using the ControlDesk software for monitoring and testing of the real plant. The latter consists of the VSI operating with LCL filters, and sharing an RL load with a paralleled VSI with exactly the same controller. Finally, the obtained experimental waveforms are shown, with our respective conclusions representing this work, which is a very valuable tool for helping microgrid researchers implement dSPACE-based real-time simulations.