Direct Gating of the TRPM2 Channel by cADPR via Specific Interactions with the ADPR Binding Pocket

cADPR is a well-recognized signaling molecule by modulating the RyRs, but considerable debate exists regarding whether cADPR can bind to and gate the TRPM2 channel, which mediates oxidative stress signaling in diverse physiological and pathological processes. Here, we show that purified cADPR evoked TRPM2 channel currents in both whole-cell and cell-free single-channel recordings and specific binding of cADPR to the purified NUDT9-H domain of TRPM2 by surface plasmon resonance. Furthermore, by combining computational modeling with electrophysiological recordings, we show that the TRPM2 channels carrying point mutations at H1346, T1347, L1379, S1391, E1409, and L1484 possess distinct sensitivity profiles for ADPR and cADPR. These results clearly indicate cADPR is a bona fide activator at the TRPM2 channel and clearly delineate the structural basis for cADPR binding, which not only lead to a better understanding in the gating mechanism of TRPM2 channel but also shed light on a cADPR-induced RyRs-independent Ca2+ signaling mechanism

Thermal properties of cubic KTa 1 x Nb x O 3 crystals

Cubic potassium tantalite niobate KTa1−xNbxO3 KTN crystals of large size, good quality, and varying Nb concentration have been grown by the Czochralski method and their thermal properties have been systematically studied. The melting point, molar enthalpy of fusion, and molar entropy of fusion of the crystals were determined to be: 1536.9 K, 12 068.521 J mol−1, and 7.85 J K−1 mol−1 for KTa0.67Nb0.33O3; and 1520.61 K, 15 352.511 J mol−1, and 10.098 J K−1 mol−1 for KTa0.67Nb0.33O3, respectively. Based on the data, the Jackson factor was calculated to be 0.994f and 1.214f for KTa0.67Nb0.33O3 and KTa0.63Nb0.37O3, respectively. The thermal expansion coefficients over the temperature range of 298.15−773.15 K are: =4.0268 10−6 /K, 6.4428 10−6 /K, 6.5853 10−6 /K for KTaO3, KTa0.67Nb0.33O3, and KTa0.63Nb0.37O3, respectively. The density follows an almost linear decrease when the temperature increases=from 298.15 to 773.15 K. The measured specific heats at 303.15 K are: 0.375 J g−1 K−1 for KTaO3; 0.421 J g−1 K−1 for KTa0.67Nb0.33O3, and 0.430 J g−1 K−1 for KTa0.63Nb0.37O3 The thermal diffusion coefficients of the crystals were measured over the temperature range from 303.15−563.15 K. The calculated thermal conductivity values of KTaO3, KTa0.67Nb0.33O3, and KTa0.63Nb0.37O3 at 303.15 K are 8.551, 5.592, and 4.489 W m−1 K−1, respectively. The variation of these thermal properties versus Nb concentration is qualitatively analyzed. These results show that crystalline KTN is a promising material for optical applications