Role of proline residue in the channel-forming and catecholamine-releasing activities of the peptaibol, trichosporin-B-VIa

AbstractTrichosporin-B-VIa (TS-B-VIa) has a Pro14-kinked helical structure which is considered to be important for the formation of peptaibol-type ion-channels in lipid bilayer membranes. TS-B-VIa and its analog [Aid14]TS-B-VIa with Pro → Aib substitution at position 14, resulting in a straight helical structure, were tested for ion-channel-forming activity in planar lipid bilayer membranes and for ability to induce catecholamine secretion from cultured bovine adrenal chromaffin cells. Voltage-dependent multi-channel conductance, which is characteristic of TS-B-VIa, was also observed for [Aid14]TS-B-VIa. In single-channel measurements, current fluctuations induced by [Aid14]TS-B-VIa had a shorter life-time and showed fewer substates than those induced by TS-B-VIa. Catecholamine secretion induced by these peptides at low concentrations is completely Ca2+-dependent. At high concentrations, TS-B-VIa-induced secretion was partly independent of external Ca 2+, but this was not the case for the analog. The differences of behavior can be explained in terms of the differences of hydrophobicity, amphiphilicity, and magnitude of dipole moment due to the conformational changes around position 14 and the C-terminal domain caused by the Pro → Aib substitution

Asymmetrical membrane fluidity of bovine adrenal chromaffin cells and granules and effect of trichosporin-B-VIa

AbstractWe examined membrane fluidity of bovine adrenal chromaffin cells and chromaffin granules using cationic trimethylammonium derivative of diphenylhexatriene (TMA-DPH) as a fluorescence probe. After adding TMA-DPH to the suspension of chromaffin cells and that of granules, it first bound to the outer layer of the plasma membrane of the cells and that of the granule membrane, then gradually penetrated the inner layer of each membrane and distributed to both leaflets of the respective membranes. Accompanying increases in the ratio of incorporated probe on the cytoplasmic side of the chromaffin cell membrane, its fluorescence anisotropy gradually decreased. However, in chromaffin granules, the fluorescence anisotropy gradually increased with increases in the ratio of incorporated probe. These findings suggest that the inner layer of the plasma membrane and outer layer of the granular membrane are more fluid than the corresponding side of each membrane, which is suitable for the fusion between both membranes. We also examined the effect of trichosporin-B-VIa, a fungal ion channel forming α-aminoisobutyric acid-containing peptide, on the fluidity of chromaffin cells using TMA-DPH. The peptide decreased the fluorescence anisotropy and increased the fluorescence intensity in the concentration range that induced Ca2+ dependent catecholamine secretion, suggesting that a change in lipid dynamics of the lipid bilayer of the plasma membrane was induced by this peptide

Fast-Ion-Diagnostics for CHS Experiment

Fast-ion-diagnostics have played an important role in investigating issues related to fast ion orbits and fast-ion-driven MHD instabilities in CHS experiments. The fast-ion diagnostics employed in CHS are reviewed and experimentally obtained knowledge is summarized

Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonists-induced orofacial dyskinesia

ジスキネジア新治療法の発見 --副作用を減らす併用薬から新しい創薬標的へ--. 京都大学プレスリリース. 2021-04-16.Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the U.S. Food and Drug Administration Adverse Event Reporting System and JMDC insurance claims revealed that acetaminophen prevents the dyskinesia induced by dopamine D₂ receptor antagonists. In vivo experiments further showed that a 21-day treatment with haloperidol increased the number of vacuous chewing movements (VCMs) in rats, an effect that was inhibited by oral acetaminophen treatment or intracerebroventricular injection of N-(4-hydroxyphenyl)-arachidonylamide (AM404), an acetaminophen metabolite that acts as an activator of the transient receptor potential vanilloid 1 (TRPV1). In mice, haloperidol-induced VCMs were also mitigated by treatment with AM404 applied to the dorsal striatum, but not in TRPV1-deficient mice. Acetaminophen prevented the haloperidol-induced decrease in the number of c-Fos⁺/preproenkephalin⁺ striatal neurons in wild-type mice but not in TRPV1-deficient mice. Finally, chemogenetic stimulation of indirect-pathway medium spiny neurons in the dorsal striatum decreased haloperidol-induced VCMs. These results suggest that acetaminophen activates the indirect pathway neurons by activating TRPV1 channels via AM404

Variation of Heating Efficiency of Magnetically Sheared CHS Plasmas by Polarization Control of 106GHz EC-Wave

To clarify the effect of polarization on electron cyclotron heating (ECH) in magnetized plasmas, experiment controlling the polarization of injected EC-waves is carried out in Compact Helical System (CHS). In the experiment, plasmas are generated and sustained only with 106.4 GHz ECH power. Magnetic field at the magnetic axis is 1.9 T so that the wave frequency is second harmonic. The optimum direction of linear polarization for the shortest time-delay of density start-up from the start of power injection and the optimum direction for the highest electron temperature and plasma stored energy during plasma duration show clear difference. The difference is attributed to the CHS magnetic configuration with strong shear and the plasma volume expansion from magnetic axis to the last closed flux surface

Determination of the Major Impurity Radiators in the Reheat Mode Discharges in the Compact Helical System

Radiation brightness and impurity behaviors have been studied for reheat mode discharges in the Compact Helical System (CHS) by three different types of impurity diagnostics. Total radiation power measured by a pyroelectric detector significantly reduces after entering the reheat mode, whereas the line-averaged radiation brightness measured by an absolute extreme ultraviolet (AXUV) photodiode array increases especially for a center viewing chord due to the impurity accumulation in the plasma core. One possible reason for this opposite behavior between the two bolometric detectors is the reduced sensitivity of the AXUV photodiode for lower energy photons in vacuum ultraviolet (VUV) region. This speculation is supported by temporal evolutions of VUV spectra measured by a grazing incidence spectrometer. These results demonstrate that the comparison of three impurity diagnostics would be beneficial to the determination of the major impurity radiators and a comprehensive understanding of impurity behaviors in the reheat mode discharges

Radial Transport Characteristics of Fast Ions Due to Energetic-Particle Modes inside the Last Closed-Flux Surface in the Compact Helical System

The internal behavior of fast ions interacting with magnetohydrodynamic bursts excited by energetic ions has been experimentally investigated in the compact helical system. The resonant convective oscillation of fast ions was identified inside the last closed-flux surface during an energetic-particle mode (EPM) burst. The phase difference between the fast-ion oscillation and the EPM, indicating the coupling strength between them, remains a certain value during the EPM burst and drives an anomalous transport of fast ions

Nano-honeycomb electrode based QCM sensor and its application for PPI detection

An anodic aluminon oxide (AAO)-based nano honeycomb electrode was coated on a quartz crystal for use as a sensing device in a quartz crystal microbalance (QCM) to monitor the protein-protein interactions (PPIs). As examples, we detected PPIs of anti-Bcl-2 and Bcl-2, and Bcl-2 and Bax in real time. A sensor with a flat Au electrode showed a tiny frequency shift upon sample injection. However, our fabricated device could detect 10 μg/mL of Bcl-2 and Bax in sequence.2016年度関西大学研究拠点形成支援経

Strong suppression of impurity accumulation in steady-state hydrogen discharges with high power NBI heating on LHD

Strong suppression of impurity accumulation is observed in long pulse hydrogen discharges with high power NBI (neutral beam injection) heating (Pnbi  >  10 MW) on the large helical device (LHD), even in the impurity accumulation window where the intrinsic impurities such as Fe and C are always accumulated into the plasma core. Density scan experiments in these discharges demonstrate to vanish the window and a new operational regime without impurity accumulation is found in steady state hydrogen discharges. Impurity pinch decreases with increasing ion temperature gradient and carbon Mach number. The peaking of the measured carbon profiles shows strong anti-correlations with the Mach number and its radial gradient. An external torque has a big impact on impurity transport and strong co-current rotation leads to an extremely hollow carbon profile, so-called \u27impurity hole\u27 observed in high ion temperature modes. Impurity pinch in the plasmas with net zero torque input (balanced NBI injection) is also strongly reduced by increasing ion temperature gradient, which can drive turbulent modes. The combination effect of turbulence and toroidal rotation plays an important role in the impurity transport