Sensitive Channels Research Articles

TRPV1 Ion Channel: Structural Features, Activity Modulators, and Therapeutic Potential.

Although TRPV1 ion channel has been attracting researchers' attention for many years, its functions in animal organisms, the principles of regulation, and the involvement in pathological processes have not yet been fully clarified. Mutagenesis experiments and structural studies have identified the structural features of the channel and binding sites for its numerous ligands; however, these studies are far from conclusion. This review summarizes recent achievements in the TRPV1 research with special focus on structural and functional studies of the channel and on its ligands, which are extremely diverse in their nature and interaction specificity to TRPV1. Particular attention was given to the effects of numerous endogenous agonists and antagonists that can fine-tune the channel sensitivity to its usual activators, such as capsaicin, heat, acids, or their combination. In addition to the pain sensing not covered in this review, the TRPV1 channel was found to be involved in the regulation of many important physiological and pathological processes and, therefore, can be considered as a promising therapeutic target in the treatment of various diseases, such as pneumonia, ischemia, diabetes, epilepsy, schizophrenia, psoriasis, etc.

Effects of calcium-activated potassium channel modulators on afterhyperpolarizing potentials in identified motor and mechanosensory neurons of the medicinal leech.

Calcium-activated potassium (KCa) channels contribute to multiple neuronal properties including spike frequency and afterhyperpolarizing potentials (AHPs). KCa channels are classified as KCa1.1, KCa2, or KCa3.1 based on single-channel conductance and pharmacology. Ca2+-dependent AHPs in vertebrates are categorized as fast, medium, or slow. Fast and medium AHPs are generated by KCa1.1 and KCa2 channels, respectively. The KCa subtype responsible for slow AHPs is unclear. Prolonged, Ca2+-dependent AHPs have been described in several leech neurons. Unfortunately, apamin and other KCa blockers often prove ineffective in the leech. An alternative approach is to utilize KCa modulators, which alter channel sensitivity to Ca2+. Vertebrate KCa2 channels are targeted selectively by the positive modulator CyPPA and the negative modulator NS8593. Here we show that AHPs in identified motor and mechanosensory leech neurons are enhanced by CyPPA and suppressed by NS8593. Our results indicate that KCa2 channels underlie prolonged AHPs in these neurons and suggest that KCa2 modulators may serve as effective tools to explore the role of KCa channels in leech physiology.

Link Quality Analysis of Wireless Sensor Networks for Underground Infrastructure Monitoring: A Non-Backfilled Scenario

Wireless underground sensor networks (WUSNs) have been preliminarily applied in underground infrastructure monitoring (UIM) to alert entities about any anomaly in a timely manner. Some key repeaters are deployed along a typical borehole to ensure reliable connectivity with the aboveground gateways. However, the link quality characteristics of the bi-directional communications between the underground repeaters and aboveground devices have not been experimentally analyzed for UIM-WUSNs. To this end, a semi-empirical evaluation of underground-to-aboveground (UG2AG) and aboveground-to-underground (AG2UG) communications are presented in non-backfilled scenarios. In this paper, the effects of burial depth, internode distance, propagation direction, and backfilled condition on link quality are quantitatively investigated by real-life experiments. First, the non-backfilled UG2AG and AG2UG channel model is proposed and verified by the measured data. Then, the symmetry between the UG2AG and AG2UG links is demonstrated in the non-backfilled communication. Finally, the backfilled UG2AG/AG2UG communications show asymmetry behavior, which is largely due to the channel sensitivity to the soil properties. These findings can provide guidelines for the design and development of new communication protocols in UIM-WUSNs.

Universal Piezoelectric Seismometer

A universal piezoelectric seismometer is proposed that can simultaneously record linear and angular accelerations through two separate channels. The operational principle of the seismometer and the features of its design are described; the mechanical and electric circuits are considered. The device uses two-element piezoelectric linear and angular acceleration sensors with a total inertial mass. The principle of addition and compensation of electric signals is implemented. The channel sensitivities are referenced to real seismic vibration values. Based on an analysis of a large number of seismic vibration records, seismometer parameters are proposed that are suitable for use in the near fields of strong earthquakes.

Dipole response of Rb87 and its impact on the Rb86(n,γ)Rb87 cross section

Background: Detailed information on the low-lying dipole response in atomic nuclei along isotonic or isotopic chains is well suited to systematically investigate the structure and evolution of the pygmy dipole resonance (PDR). Moreover, the dipole strength below and around the neutron separation energy Sn has impact on statistical model calculations for nucleosynthesis processes. Purpose: The photon strength function (PSF) of Rb87, which is directly connected to the photoabsorption cross section, is a crucial input for statistical model calculations constraining the Maxwellian-averaged cross section (MACS) of the neutron capture of the unstable s-process branching-point nucleus Rb86. Within this work, the photoabsorption cross section is investigated. Methods: The photoabsorption cross section of the N=50 nucleus Rb87 was determined from photon-scattering experiments via the nuclear resonance fluorescence (NRF) technique. Bremsstrahlung beams at the γELBE facility in conjunction with monoenergetic photon beams at the HIγS facility were used to determine the integrated cross sections Is of isolated states as well as the averaged cross section as function of the excitation energy. Decays to the ground state were disentangled from decays to first low-lying excited states. Statistical and experimental approaches for the γ-decay properties at various excitation energies were applied. The linearly polarized photon beams at HIγS provide information on the ratio of electric and magnetic type of radiation. Results: Within this work, more than 200 ground-state decays and associated levels in Rb87 were identified. Moreover, transitions below the sensitivity limit of the state-by-state analysis were taken into account via a statistical approach from the bremsstrahlung data as well as model-independently from the HIγS data. The photoabsorption cross sections at various excitation energies were determined. The dipole response between 6 and 10 MeV of Rb87 is in agreement with assuming contributions of electric multipolarity, only. Conclusions: The photoabsorption cross section of Rb87 does not contradict with the trend of decreasing E1 strength with increasing proton number along the N=50 isotonic chain but might also be associated with a constant trend. The experimental γ decay at various excitation energies of the HIγS data supports the statistical approach but does not provide a stringent proof due to the limited sensitivity in the decay channels. The additional E1 strength observed in the present experiments significantly enhances the MACSs compared only to recent microscopic HFB+QRPA (Hartree-Fock-Bogoliubov plus quasiparticle random-phase approximation) calculations using the D1M interaction. Moreover, theoretical estimations provided by the KADoNiS project could be significantly improved.6 MoreReceived 18 June 2020Revised 24 August 2020Accepted 28 September 2020DOI:https://doi.org/10.1103/PhysRevC.102.044327©2020 American Physical SocietyPhysics Subject Headings (PhySH)Research AreasElectromagnetic transitionsEnergy levels & level densitiesNuclear astrophysicsPhotonuclear reactionsRadiative captureProperties59 ≤ A ≤ 89Nuclear Physics

Clinical worsening due to inappropriate automatic mode switch during biventricular pacing: What is the mechanism?

We describe a case of a 65-year-old gentleman with nonischemic cardiomyopathy and left bundle branch block who underwent cardiac resynchronization therapy device. After becoming a responder initially, he experienced significant clinical worsening on follow-up. Device interrogation revealed several long episodes of inappropriate automatic mode switch (AMS) entry due to far-field R wave oversensing resulting in loss of atrioventricular synchrony. Moreover, pacing in VVI mode with consistent VA conduction taking place during the AMS episodes was also found to be detrimental, which helped in sustaining the episodes and produced pacemaker syndrome like phenomenon. Attempts made to resolve the issue by prolonging the post-ventricular atrial blanking period was unsuccessful, hence we adjusted the atrial channel sensitivity to troubleshoot the problem.

Hydrophobic interactions between the HA helix and S4-S5 linker modulate apparent Ca2+ sensitivity of SK2 channels.

Small-conductance Ca2+ -activated potassium (SK) channels are activated exclusively by increases in intracellular Ca2+ that binds to calmodulin constitutively associated with the channel. Wild-type SK2 channels are activated by Ca2+ with an EC50 value of ~0.3μmol/L. Here, we investigate hydrophobic interactions between the HA helix and the S4-S5 linker as a major determinant of channel apparent Ca2+ sensitivity. Site-directed mutagenesis, electrophysiological recordings and molecular dynamic (MD) simulations were utilized. Mutations that decrease hydrophobicity at the HA-S4-S5 interface lead to Ca2+ hyposensitivity of SK2 channels. Mutations that increase hydrophobicity result in hypersensitivity to Ca2+ . The Ca2+ hypersensitivity of the V407F mutant relies on the interaction of the cognate phenylalanine with the S4-S5 linker in the SK2 channel. Replacing the S4-S5 linker of the SK2 channel with the S4-S5 linker of the SK4 channel results in loss of the hypersensitivity caused by V407F. This difference between the S4-S5 linkers of SK2 and SK4 channels can be partially attributed to I295 equivalent to a valine in the SK4 channel. A N293A mutation in the S4-S5 linker also increases hydrophobicity at the HA-S4-S5 interface and elevates the channel apparent Ca2+ sensitivity. The double N293A/V407F mutations generate a highly Ca2+ sensitive channel, with an EC50 of 0.02μmol/L. The MD simulations of this double-mutant channel revealed a larger channel cytoplasmic gate. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca2+ sensitivity of SK2 channels.

Ensuring Dynamic Accuracy of Aircraft’s Air Data System with Motionless Flush-Mounted Receiver of Flow

The article views, that draw-backs of aircraft’s traditional air data systems (ADS), built based installed in incoming air flow and installed outside the fuselage the pitot tube booms, temperature braking receivers, vane sensors of incidence angle and gliding angle are eliminated in original ADS with motionless flush-mounted receiver of flow. The functional scheme of aircraft’s air data system with motionless flush-mounted receiver of flow, built based on the original ion-mark sensor of aerodynamic angle and true airspeed, on receiving board of which the hole-receiver is installed to perceive the static pressure of incoming air flow. Models of operator sensitivity and dynamic errors of instrumentation channels due to random stationary atmospheric turbulence and random flow pulsations at location of the ion-mark sensor on fuselage of the aircraft are presented. Recommended to use the optimal linear Wiener filter, the synthesis method of which is revealed on example of the true airspeed instrumentation channel to reduce the stationary dynamic errors of instrumentation channels of air data system with motionless flush-mounted receiver due to atmospheric turbulence. Recommended to use the principle of integration to reduce the stationary random dynamic errors of instrumentation channels of air data system with motionless flush-mounted receiver due to flow pulsations near fuselage at location of ion-mark sensor. Proposed to use aeromechanical measuring and computing system built based VIMI method with Luenberger observer as an additional component of integrated air data system. Integrated system simulates the movement of aircraft in this flight mode and by flight parameters measured with high accuracy using flush-mounted receivers "restores" air signals included in equations of movement of aircraft. The structure, method and algorithms for determining air signals in channels of aeromechanical measuring and computing system with a Luenberger observer are presented. Using the example of true airspeed measurement, the analysis and quantitative assessment of residual dynamic error of integrating channel of integrated aircraft’s air data system with motionless flush-mounted receiver of flow is carried out.

PH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology.

Tissue acidosis plays a pivotal role in tumor progression: in particular, interstitial acidosis promotes tumor cell invasion, and is a major contributor to the dysregulation of tumor immunity and tumor stromal cells. The cell membrane and integral membrane proteins commonly act as important sensors and transducers of altered pH. Cell adhesion molecules and cation channels are prominent membrane proteins, the majority of which is regulated by protons. The pathophysiological consequences of proton-sensitive ion channel function in cancer, however, are scarcely considered in the literature. Thus, the main focus of this review is to highlight possible events in tumor progression and tumor immunity where the pH sensitivity of cation channels could be of great importance.

Overexpression of phosphatidylserine synthase IbPSS1 affords cellular Na+ homeostasis and salt tolerance by activating plasma membrane Na+/H+ antiport activity in sweet potato roots

Phosphatidylserine synthase (PSS)-mediated phosphatidylserine (PS) synthesis is crucial for plant development. However, little is known about the contribution of PSS to Na+ homeostasis regulation and salt tolerance in plants. Here, we cloned the IbPSS1 gene, which encodes an ortholog of Arabidopsis AtPSS1, from sweet potato (Ipomoea batatas (L.) Lam.). The transient expression of IbPSS1 in Nicotiana benthamiana leaves increased PS abundance. We then established an efficient Agrobacterium rhizogenes-mediated in vivo root transgenic system for sweet potato. Overexpression of IbPSS1 through this system markedly decreased cellular Na+ accumulation in salinized transgenic roots (TRs) compared with adventitious roots. The overexpression of IbPSS1 enhanced salt-induced Na+/H+ antiport activity and increased plasma membrane (PM) Ca2+-permeable channel sensitivity to NaCl and H2O2 in the TRs. We confirmed the important role of IbPSS1 in improving salt tolerance in transgenic sweet potato lines obtained from an Agrobacterium tumefaciens-mediated transformation system. Similarly, compared with the wild-type (WT) plants, the transgenic lines presented decreased Na+ accumulation, enhanced Na+ exclusion, and increased PM Ca2+-permeable channel sensitivity to NaCl and H2O2 in the roots. Exogenous application of lysophosphatidylserine triggered similar shifts in Na+ accumulation and Na+ and Ca2+ fluxes in the salinized roots of WT. Overall, this study provides an efficient and reliable transgenic method for functional genomic studies of sweet potato. Our results revealed that IbPSS1 contributes to the salt tolerance of sweet potato by enabling Na+ homeostasis and Na+ exclusion in the roots, and the latter process is possibly controlled by PS reinforcing Ca2+ signaling in the roots.

Neonatal diabetes due to potassium channel mutation: Response to sulfonylurea according to the genotype.

A precision medicine approach is used to improve treatment of patients with monogenic diabetes. Herein, we searched SU efficiency according to the genotype-phenotype correlation, dosage used, and side effects. Systematic review conducted according the PRISMA control criteria identifying relevant studies evaluating the in vivo and in vitro sensitivity of ATP-dependent potassium channels according to the characteristics of genetic mutation. Hundred and three selected articles with complete data in 502 cases in whom 413 (82.3%) had mutations in KCNJ11 (#64) and 89 in ABCC8 (# 56). Successful transfer from insulin to SU was achieved in 91% and 86.5% patients, respectively, at a mean age of 36.5 months (0-63 years). Among patients with KCNJ11 and ABCC8 mutations 64 and 46 were associated with constant success, 5 and 5 to constant failure, and 10 and 4 to variable degrees of reported success rate, respectively. The glibenclamide dosage required for each genotype ranged from 0.017 to 2.8 mg/kg/day. Comparing both the in vivo and in vitro susceptibility results, some mutations appear more sensitive than others to sulfonylurea treatment. Side effects were reported in 17/103 of the included articles: mild gastrointestinal symptoms and hypoglycaemia were the most common. One premature patient had an ulcerative necrotizing enterocolitis which association with SU is difficult to ascertain. Sulfonylureas are an effective treatment for monogenic diabetes due to KCNJ11 and ABCC8 genes mutations. The success of the treatment is conditioned by differences in pharmacogenetics, younger age, pharmacokinetics, compliance, and maximal dose used.

Response surface methodology of dual-channel green supply-chain pricing model by considering uncertainty

ABSTRACT Companies apply dual-channel supply-chain (DCSC) by allocating online facilities without leaving conventional retailers. As a result, carbon emissions from production activities have increased in the company structure. Nowadays, DCSC researchers have a tendency to set their models in deterministic settings. These models cannot cope with the structure complexity. This research used Response Surface Methodology to analyse uncertainty in DCSC. The decision variables were the retailers and online prices, while the responses were price channel sensitivities (βo and βr), cross-channel sensitivities (γor and γro), profit estimation, and carbon emission estimation. In illustrating the real-world competition under oligopoly games, the optimisation phase used nonlinear programming under cooperative and non-cooperative scenarios. The result showed that in each channel, price combination had a significant effect on the response variables. Price differences on each channel could confirm the changes of customer preference channel. This study finds that the application of a response surface methodology can describe the significance of price to the DCSC system.

WALLABY – an SKA Pathfinder H i survey

The Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) is a next-generation survey of neutral hydrogen (HI) in the Local Universe. It uses the widefield, high-resolution capability of the Australian Square Kilometer Array Pathfinder (ASKAP), a radio interferometer consisting of 36 x 12-m dishes equipped with Phased-Array Feeds (PAFs), located in an extremely radio-quiet zone in Western Australia. WALLABY aims to survey three-quarters of the sky (-90 degr < Dec < +30 degr) to a redshift of z < 0.26, and generate spectral line image cubes at ~30 arcsec resolution and ~1.6 mJy/beam per 4 km/s channel sensitivity. ASKAP's instantaneous field of view at 1.4 GHz, delivered by the PAF's 36 beams, is about 30 sq deg. At an integrated signal-to-noise ratio of five, WALLABY is expected to detect over half a million galaxies with a mean redshift of z ~ 0.05 (~200 Mpc). The scientific goals of WALLABY include: (a) a census of gas-rich galaxies in the vicinity of the Local Group; (b) a study of the HI properties of galaxies, groups and clusters, in particular the influence of the environment on galaxy evolution; and (c) the refinement of cosmological parameters using the spatial and redshift distribution of low-bias gas-rich galaxies. For context we provide an overview of previous large-scale HI surveys. Combined with existing and new multi-wavelength sky surveys, WALLABY will enable an exciting new generation of panchromatic studies of the Local Universe. - First results from the WALLABY pilot survey are revealed, with initial data products publicly available in the CSIRO ASKAP Science Data Archive (CASDA).

Three sodium channel mutations from Aedes albopictus confer resistance to Type I, but not Type II pyrethroids

Voltage-gated sodium channels are the major targets of several classes of insecticides, including pyrethroids. However, sensitivities of many insect pest species to pyrethroids have gradually decreased due to overuse in pest management programs. One major mechanism of pyrethroid resistance known as knockdown resistance (kdr) involves mutations in the sodium channel gene. Three new mutations in helix IIIS6 of sodium channel (I1532T and F1534S/L) are recently detected in several pyrethroid-resistant populations of Aedes albopictus. The roles of these mutations in pyrethroid resistance have not been functionally examined. We introduced mutations I1532T and F1534S/L alone or in combination into the pyrethroid-sensitive sodium channel AaNav1-1 from Aedes aegypti by site-directed mutagenesis and explored effects of these mutations on the channel gating and sensitivity to pyrethroids. No significant modifications in channel properties were detected, except for a slightly changed activation by F1534S and I1532T + F1534S. However, I1532T and F1534S/L substantially reduced the channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, but not to two Type II pyrethroids, deltamethrin and cypermethrin. The double mutations did not increase the channel resistance to permethrin or bifenthrin. We have built a Nav1.4-based homology model of the AaNav1-1 channel and docked pyrethroids in the model to explain different sensitivities of the mutants to Type I and Type II pyrethroids. The results will assist in developing molecular markers for monitoring pest resistance to pyrethroids. They also provide new insight in the molecular basis of different action of Type I and Type II pyrethroids on sodium channels.

Delineating an extracellular redox-sensitive module in T-type Ca2+ channels

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.

Person identification using EEG channel selection with hybrid flower pollination algorithm

Recently, electroencephalogram (EEG) signal presents a great potential for a new biometric system to deal with a cognitive task. Several studies defined the EEG with uniqueness features, universality, and natural robustness that can be used as a new track to prevent spoofing attacks. The EEG signals are the graphical recording of the brain electrical activities which can be measured by placing electrodes (channels) in various positions of the scalp. With a large number of channels, some channels have very important information for biometric system while others not. The channel selection problem has been recently formulated as an optimisation problem and solved by optimisation techniques. This paper proposes hybrid optimisation techniques based on binary flower pollination algorithm (FPA) and β-hill climbing (called FPAβ-hc) for selecting the most relative EEG channels (i.e., features) that come up with efficient accuracy rate of personal identification. Each EEG signals with three different groups of EEG channels have been utilized (i.e., time domain, frequency domain, and time-frequency domain). The FPAβ-hc is measured using a standard EEG signal dataset, namely, EEG motor movement/imagery dataset with a real world data taken from 109 persons each with 14 different cognitive tasks using 64 channels. To evaluate the performance of the FPAβ-hc, five measurement criteria are considered:accuracy (Acc), (ii) sensitivity (Sen), (iii) F-score (F_s), (v) specificity (Spe), and (iv) number of channels selected (No. Ch). The proposed method is able to identify the personals with high Acc, Sen., F_s, Spe, and less number of channels selected. Interestingly, the experimental results suggest that FPAβ-hc is able to reduce the number of channels with accuracy rate up to 96% using time-frequency domain features. For comparative evaluation, the proposed method is able to achieve results better than those produced by binary-FPA-OPF method using the same EEG motor movement/imagery datasets. In a nutshell, the proposed method can be very beneficial for effective use of EEG signals in biometric applications.

Influence of RGS6 on Inhibitory G Protein Signaling in Mouse Sinoatrial Nodal Cells

IntroductionM2 muscarinic (M2R) activation of G protein‐gated inwardly rectifying K+ (GIRK) channels in sinoatrial nodal (SAN) cells is a key mediator of vagal/parasympathetic slowing of heart rate. The strength of M2R‐GIRK signaling is negatively regulated by Regulator of G protein Signaling 6 (RGS6). Adenosine, used clinically to diagnose and treat certain arrhythmias, exerts these actions through A1 adenosine receptor (A1R) activation of GIRK channels. The extent to which RGS6 regulates A1R‐GIRK signaling, however, is unclear. Here, we investigated the impact of RGS6 on A1R‐GIRK and M2R‐GIRK signaling in mouse SAN cells.Methods and ResultsWe measured the efficacy and potency of M2R‐ and A1R‐GIRK signaling in adult SAN cells from wild‐type and RGS6−/− mice using whole‐cell patch‐clamp electrophysiology. As previously reported, SAN cells from RGS6−/− mice displayed prolonged channel deactivation kinetics and increased channel sensitivity to the non‐selective cholinergic agonist carbachol (CCh), relative to wild‐type counterparts. In contrast, we observed a striking increase in the amplitude of the GIRK response evoked by adenosine (Ado) in RGS6−/− SAN cells compared to wild‐type controls, with no impact on channel deactivation kinetics or sensitivity. Further recordings in wild‐type SAN cells revealed that M2R activation completely occludes the Ado‐induced response, whereas Ado application activates only a smaller fraction of GIRK channels. Both CCh‐ and Ado‐ induced currents were abolished in SAN cells treated by pertussis toxin (PTX), indicating these responses are mediated by Gi/o G proteins. Utilizing a bioluminescence resonance energy transfer (BRET) assay in transfected HEK cells, we found that RGS6 prefers Gαo as a substrate for over Gαi. Additionally, we found that while A1R does not discriminate between Gαo and Gαi, M2R displays a clear preference for Gαo. We next employed a Cre/flox strategy to remove Gαo from atrial tissue, including SAN cells. Loss of Gαo yielded significantly blunted CCh‐induced responses, which also displayed prolonged activation and deactivation kinetics. While Ado‐induced responses had prolonged deactivation kinetics, activation kinetics and response amplitude were unaffected.ConclusionsThese results suggest that RGS6 negatively regulates A1R‐GIRK signaling distinct from its influence on M2R‐GIRK signaling in mouse SAN cells likely due to differing utilization of Gao by M2R and A1R.Support or Funding InformationThis work was supported by NIH grants R01 HL105550 and F31 HL139090.

Additional Calibration of the Ultraviolet Imaging Telescope on Board AstroSat

Abstract Results of the initial calibration of the Ultra-Violet Imaging Telescope (UVIT) were reported earlier by Tandon et al. The results reported earlier were based on the ground calibration as well as the first observations in orbit. Some additional data from the ground calibration and data from more in-orbit observations have been used to improve the results. In particular, extensive new data from in-orbit observations have been used to obtain (a) new photometric calibration that includes (i) zero points, (ii) flat fields, and (iii) saturation; (b) sensitivity variations; (c) spectral calibration for the near ultraviolet (NUV; 2000–3000 Å) and far ultraviolet (FUV; 1300–1800 Å) gratings; (d) point-spread function; and (e) astrometric calibration including distortion. Data acquired over the last three years show continued good performance of UVIT with no reduction in sensitivity in both UV channels.

Engineering an enhanced voltage-sensing phosphatase.

Voltage-sensing phosphatases (VSP) consist of a membrane-spanning voltage sensor domain and a cytoplasmic region that has enzymatic activity toward phosphoinositides (PIs). VSP enzyme activity is regulated by membrane potential, and its activation leads to rapid and reversible alteration of cellular PIP levels. These properties enable VSPs to be used as a tool for studying the effects of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) binding to ion channels and transporters. For example, by applying simple changes in the membrane potential, Danio rerio VSP (Dr-VSP) has been used effectively to manipulate PI(4,5)P2 in mammalian cells with few, if any, side effects. In the present study, we report an enhanced version of Dr-VSP as an improved molecular tool for depleting PI(4,5)P2 from cultured mammalian cells. We modified Dr-VSP in two ways. Its voltage-dependent phosphatase activity was enhanced by introducing an aromatic residue at the position of Leu-223 within a membrane-interacting region of the phosphatase domain called the hydrophobic spine. In addition, selective plasma membrane targeting of Dr-VSP was facilitated by fusion with the N-terminal region of Ciona intestinalis VSP. This modified Dr-VSP (CiDr-VSPmChe L223F, or what we call eVSP) induced more drastic voltage-evoked changes in PI(4,5)P2 levels, using the activities of Kir2.1, KCNQ2/3, and TRPC6 channels as functional readouts. eVSP is thus an improved molecular tool for evaluating the PI(4,5)P2 sensitivity of ion channels in living cells.

A locally segmented reconstruction method for parallel imaging.

A locally segmented parallel imaging reconstruction method is proposed that efficiently utilizes sensitivity distribution of multichannel receiver coil. A method of locally segmenting a MR signal is introduced to maximize the differences in sensitivity between receiver channels. A 1D Fourier transformation of the undersampled k-space data is performed along the readout direction, which generates a hybrid 2D space. The hybrid space is partitioned into localized segments along the readout direction. In every localized segment, kernels representing relation between adjacent signals are estimated from autocalibration signals, and data at unsampled points are estimated using the kernels. Then, the images are reconstructed from full k-space data that consists of the sampled data and the estimated data at unsampled points. In a computer simulation and in vivo experiments, the locally segmented reconstruction method produced fewer residual artifacts compared to the conventional parallel imaging reconstruction methods with the same kernel geometry. The performance gain of the proposed method comes from maximizing encoding capability of receiver channels, thus resulting in the accurately estimated kernel weights that reflect the relation between adjacent signals. The proposed spatial segmentation method maximally utilizes differences in the sensitivity of receiver channels to reconstruct images with reduced artifacts.