These results indicate that our torsadogenic risk assessment is reliable and has a potential to replace the hERG assay for torsadogenic risk prediction, however, this system needs to be improved for the accurate of prediction of clinical TdP risk. Here, we propose a novel drug induced torsadogenic risk categorising system using hiPSC-CMs and the MEA system.

FP can be used to assess the QT prolongation and proarrhythmic potential of drug candidates; however, experimental conditions such as HPF frequency are important for obtaining reliable data.

No abstract

The streaming potential (V stream) is a signature feature of ion channels in which permeating ions and water molecules move in a single file. V stream provides a quantitative measure of the ion and water flux (the water–ion coupling ratio), the knowledge of which is a prerequisite for elucidating the mechanisms of ion permeation. We have developed a method to measure V stream with the whole-cell patch-clamp configuration. A HEK293 cell stably expressing the HERG potassium channel was voltage clamped and exposed to hyperosmotic solutions for short periods of time (<1 s) by an ultrafast solution switching system (the osmotic pulse [quick jump-and-away] method). The reversal potentials were monitored by a series of voltage ramps before, during, and after the osmotic pulse. The shifts of the reversal potentials immediately after the osmotic jump gave V stream. In symmetrical K+ solutions (10 mM), the V streams measured at different osmolalities showed a linear relationship with a slope of −0.7 mV/ΔOsm, from which the water–ion coupling ratio (n, the ratio of the flux of water to the flux of cations; Levitt, D.G., S.R. Elias, and J.M. Hautman. 1978. Biochim. Biophys. Acta. 512:436–451) was calculated to be 1.4. In symmetrical 100 mM K+ solutions, the coupling ratio was decreased significantly (n = 0.9), indicating that the permeation process through states with increased ion occupancy became significant. We presented a diagrammatic representation linking the water–ion coupling ratio to the mode of ion permeation and suggested that the coupling ratio of one may represent the least hydrated ion flux in the single-file pore.

No abstract

La3+ and N co-doped TiO2, which contained paramagnetic N species, decomposed acetaldehyde under visible light irradiation. The number of the paramagnetic N species seemed to control the absorption of visible light and the activity.

Powders of TiO2 doped with a metal ion and N species were prepared by a polymerized complex method and the visible-light photocatalytic activities of the products are investigated. Of the metal ions studied (K+, Ca2+, Sr2+, Ba2+, Nb5+, Fe3+, Zn2+, and Al3+), the photocatalyst prepared with Sr2+ exhibits the highest activity for acetaldehyde decomposition under visible-light irradiation. Results obtained from x-ray photoelectron spectroscopy (XPS) and electron spin resonance (ESR) analyses suggest that the doped N species reside at interstitial lattice positions in the catalyst. It was also found by XPS and ESR measurements that the doped N species combine with lattice oxygen to give rise to a paramagnetic property. The visible-light response of the catalyst is driven by the formation of paramagnetic N species at interstitial positions in the TiO2 lattice.

Voltage-gated proton channels are found in many different types of cells, where they facilitate proton movement through the membrane. The mechanism of proton permeation through the channel is an issue of long-term interest, but it remains an open question. To address this issue, we examined the temperature dependence of proton permeation. Under whole cell recordings, rapid temperature changes within a few milliseconds were imposed. This method allowed for the measurement of current amplitudes immediately before and after a temperature jump, from which the ratios of these currents (Iratio) were determined. The use of Iratio for evaluating the temperature dependence minimized the contributions of factors other than permeation. Temperature jumps of various degrees (ΔT, −15 to 15°C) were applied over a wide temperature range (4–49°C), and the Q10s for the proton currents were evaluated from the Iratios. Q10 exhibited a high temperature dependence, varying from 2.2 at 10°C to 1.3 at 40°C. This implies that processes with different temperature dependencies underlie the observed Q10. A novel resistivity pulse method revealed that the access resistance with its low temperature dependence predominated in high temperature ranges. The measured temperature dependence of Q10 was decomposed into Q10 of the channel and of the access resistances. Finally, the Q10 for proton permeation through the voltage-gated proton channel itself was calculated and found to vary from 2.8 at 5°C to 2.2 at 45°C, as expected for an activation enthalpy of 64 kJ/mol. The thermodynamic features for proton permeation through proton-selective channels were discussed for the underlying mechanism.