Differential voltage-dependent modulation of the ACh-gated K+ current by adenosine and acetylcholine

Inhibitory regulation of the heart is determined by both cholinergic M2 receptors (M2R) and adenosine A1 receptors (A1R) that activate the same signaling pathway, the ACh-gated inward rectifier K+ (KACh) channels via Gi/o proteins. Previously, we have shown that the agonist-specific voltage sensitivity of M2R underlies several voltage-dependent features of IKACh, including the ‘relaxation’ property, which is characterized by a gradual increase or decrease of the current when cardiomyocytes are stepped to hyperpolarized or depolarized voltages, respectively. However, it is unknown whether membrane potential also affects A1R and how this could impact IKACh. Upon recording whole-cell currents of guinea-pig cardiomyocytes, we found that stimulation of the A1R-Gi/o-IKACh pathway with adenosine only caused a very slight voltage dependence in concentration-response relationships (~1.2-fold EC50 increase with depolarization) that was not manifested in the relative affinity, as estimated by the current deactivation kinetics (τ = 4074 ± 214 ms at -100 mV and τ = 4331 ± 341 ms at +30 mV; P = 0.31). Moreover, IKACh did not exhibit relaxation. Contrarily, activation of the M2R-Gi/o-IKACh pathway with acetylcholine induced the typical relaxation of the current, which correlated with the clear voltage-dependent effect observed in the concentration-response curves (~2.8-fold EC50 increase with depolarization) and in the IKACh deactivation kinetics (τ = 1762 ± 119 ms at -100 mV and τ = 1503 ± 160 ms at +30 mV; P = 0.01). Our findings further substantiate the hypothesis of the agonist-specific voltage dependence of GPCRs and that the IKACh relaxation is consequence of this property.

Piezoelectric Voltage Constant and Sensitivity Enhancements Through Phase Boundary Structure Control of Lead-free (K,Na)NbO3-based ceramics

The piezoelectric voltage constant (g33) is a material parameter critical to piezoelectric voltage-type sensors for detecting vibrations or strains. Here, we report a lead-free (K,Na)NbO3 (KNN)-based piezoelectric accelerometer with voltage sensitivity enhanced by taking advantage of a high g33. To achieve a high g33, the magnitudes of piezoelectric charge constant d33 and dielectric permittivity er of KNN were best coupled by manipulating the intrinsic polymorphic phase boundaries effectively with the help of Bi-based perovskite oxide additives. For the KNN composition that derives benefit from the combination of er and d33, the value of g33 was found to be 46.9 ´ 10-3 V·m/N, which is significantly higher than those (20 - 30 ´ 10−3 V·m/N) found in well-known polycrystalline lead-based ceramics including commercial Pb(Zr,Ti)O3 (PZT). Finally, the accelerometer sensor prototype built using the modified KNN composition demonstrated higher voltage sensitivity (183 mV/g) when measuring vibrations, showing a 29% increase against the PZT-based sensor (142 mV/g).

Chemical Targeting of Rhodol Voltage Sensitive Dyes to Dopaminergic Neurons

Optical imaging of changes in membrane potential of living cells can be achieved by the means of fluorescent voltage sensitive dyes (VSDs). A particularly challenging task is to efficiently deliver these highly lipophilic probes to specific neuronal subpopulations in brain tissue. We have tackled this task by designing a solubilizing, hydrophilic polymer platform that carries a high-affinity ligand for a membrane protein marker of interest and a fluorescent VSD. Here, we disclose an improved design of polymer supported probes for chemical, non-genetic targeting of voltage sensors to axons natively expressing the dopamine transporter in ex vivo mouse brain tissue. We first show that for negatively charged rhodol VSDs functioning on the photoinduced electron transfer principle, poly(ethylene glycol) (PEG) as a carrier enables targeting with higher selectivity than the polysaccharide dextran in HEK cell culture. In the same experimental setting, we also demonstrate that incorporation of an azetidine ring in the rhodol chromophore substantially increases the brightness and voltage sensitivity of the respective VSD. We show that the superior properties of the optimized sensor are transferable to recording of electrically evoked activity from dopaminergic axons in mouse striatal slices after averaging of multiple trials. Finally, we suggest the next milestones for the field to achieve single-scan recordings with non-genetically targeted VSDs in native brain tissue.

The Study of the Effect of Capacity Increase and Photovoltaic Placement on Power Loss, Voltage Profile by Considering THDv

The application of Photovoltaic (PV) is one solution to the increasing demand for electrical energy. However, the application of photovoltaic (PV) must be in the right location and capacity so that the power loss you want to reduce is large and the voltage profile is good. Photovoltaic (PV) generates DC voltage which is then required by an inverter to convert it to AC. The inverter is a non-linear load that produces harmonics. Harmonics in an electric power system can be known from Total Harmonic Distortion (THD). The purpose of this study is to determine the optimal location of placement (PV) and its maximum capacity so that the power loss is smaller. The resulting voltage and THD profile conform to the permitted standards. The methods used in determining the optimal location of photovoltaic (PV) are Loss Sensitivity Factor (LSF) and Voltage Sensitivity Index (VSI). ETAP 16 software is used for power and harmonic flow simulation. From this research, the most optimal photovoltaic (PV) placement is on bus 10 (bus 283 T) with a maximum capacity of 3255 kVA. This placement location provides minimal power loss and a good voltage profile taking into account the permitted standard THDv.

Predictive Control-Based NADIR-Minimizing Algorithm for Solid-State Transformer

Solid-state transformers (SSTs) are becoming an important solution to control active distribution systems. Their significant flexibility in comparison with traditional magnetic transformers is essential to ensure power quality and protection coordination at the distribution level in scenarios of large penetration of distributed energy resources such as renewables, electric vehicles and energy storage. However, the power electronic interface of SSTs decouples the nature of the inertial and frequency responses of distribution loads, deteriorating the frequency stability, especially under the integration of large-scale solar and wind power plants. Despite the virtual inertia/voltage sensitivity-based algorithms that have been proposed, the frequency sensitivity of loads and the capability of guaranteeing optimal control, considering the operating restrictions, have been overlooked. To counteract this specific issue, this work proposes a predictive control-driven approach to provide SSTs with frequency response actions by a strategy that harnesses the voltage and frequency sensibility of distribution loads and considers the limitations of voltage and frequency given by grid codes at distribution grids. In particular, the control strategy is centered in minimizing the NADIR of frequency transients. Numerical results are attained employing an empirically-validated model of the power system frequency dynamics and a dynamic model of distribution loads. Through proportional frequency control, the results of the proposed algorithm are contrasted. It is demonstrated that the NADIR improved about 0.1 Hz for 30% of SST penetration.

Differential recognition of opioid analgesics by µ opioid receptors: Predicted interaction patterns correlate with ligand-specific voltage sensitivity

The µ opioid receptor (MOR) is the key target for analgesia, but the application of opioids is accompanied by several issues. There is a wide range of opioid analgesics, differing in their chemical structure and their properties in receptor activation and subsequent effects. A better understanding of ligand-receptor interactions and resulting effects is important. Here, we calculated the respective binding modes for several opioids and analyzed fingerprints of ligand-receptor interactions. We further corroborated the binding modes experimentally by cellular assays. As ligand-induced modulation of activity due to changes in membrane potential was displayed by MOR, we further analyzed the effects of voltage sensitivity of this receptor. With a combined in silico and in vitro approach, we defined discriminating interaction patterns for the ligand-specific voltage sensitivity. With this, we present new insights for interactions likely in ligand recognition and their specific effects on activation of the MOR.

Fabrication and Characterization of Self-Powered Photosensor Based on Nanostructure TiO2/natural Dyes

Self-powered photosensor is fabricated based on nanostructure TiO2/natural dyes. TiO2 nanostructured thin film was prepared on FTO/glass substrates by hydrothermal method. Surface morphology, crystalline structure, as well as optical properties of the prepared sample are investigated. Three types of natural dyes, pomegranate, aubergine, and coffee are used as an active layer (absorber) of the fabricated photosensor. However, the solution of dye was casted onto TiO2 and left to dry naturally and carbon/FTO was used as a back contact of the device. Current-voltage (I-V) characteristic under dark and light case was characterized for all prepared sensors. Besides, the fabricated sensors appeared good response to whit light under zero bias voltage. Sensitivity, raise and decay time of the prepared photosensor are calculated.

Voltage Imaging in Drosophila Using a Hybrid Chemical-Genetic Rhodamine Voltage Reporter

We combine a chemically-synthesized, voltage-sensitive fluorophore with a genetically encoded, self-labeling enzyme to enable voltage imaging in Drosophila melanogaster. Previously, we showed that a rhodamine voltage reporter (RhoVR) combined with the HaloTag self-labeling enzyme could be used to monitor membrane potential changes from mammalian neurons in culture and brain slice. Here, we apply this hybrid RhoVR-Halo approach in vivo to achieve selective neuron labeling in intact fly brains. We generate a Drosophila UAS-HaloTag reporter line in which the HaloTag enzyme is expressed on the surface of cells. We validate the voltage sensitivity of this new construct in cell culture before driving expression of HaloTag in specific brain neurons in flies. We show that selective labeling of synapses, cells, and brain regions can be achieved with RhoVR-Halo in either larval neuromuscular junction (NMJ) or in whole adult brains. Finally, we validate the voltage sensitivity of RhoVR-Halo in fly tissue via dual-electrode/imaging at the NMJ, show the efficacy of this approach for measuring synaptic excitatory post-synaptic potentials (EPSPs) in muscle cells, and perform voltage imaging of carbachol-evoked depolarization and osmolarity-evoked hyperpolarization in projection neurons and in interoceptive subesophageal zone neurons in fly brain explants following in vivo labeling. We envision the turn-on response to depolarizations, fast response kinetics, and two-photon compatibility of chemical indicators, coupled with the cellular and synaptic specificity of genetically-encoded enzymes, will make RhoVR-Halo a powerful complement to neurobiological imaging in Drosophila.