Studying Brugada syndrome with an SCN1B variants in human-induced pluripotent stem cell-derived cardiomyocytes

BACKGROUND: Among rare channelopathies BrS patients are at high risk of sudden cardiac death (SCD). SCN5A mutations are found in a quarter of patients. Other rare gene mutations including SCN1B have been implicated to BrS. Studying the human cellular phenotype of BrS associated with rare gene mutation remains lacking. OBJECTIVES: We sought to study the cellular phenotype of BrS with the SCN1B gene variants using human-induced pluripotent stem cell (hiPSCs)–derived cardiomyocytes (hiPSC-CMs). METHODS AND RESULTS: A BrS patient suffering from recurrent syncope harboring a two variants (c.629T > C and c.637C > A) in SCN1B, which encodes the function-modifying sodium channel beta1 subunit, and three independent healthy subjects were recruited and their skin biopsies were used to generate hiPSCs, which were differentiated into cardiomyocytes (hiPSC-CMs) for studying the cellular electrophysiology. A significantly reduced peak and late sodium channel current (I(Na)) and a shift of activation curve to more positive potential as well as a shift of inactivation curve to more negative potential were detected in hiPSC-CMs of the BrS patient, indicating that the SCN1B variants impact the function of sodium channels in cardiomyocytes. The reduced I(Na) led to a reduction of amplitude (APA) and upstroke velocity (V(max)) of action potentials. Ajmaline, a sodium channel blocker, showed a stronger effect on APA and Vmax in BrS cells as compared to cells from healthy donors. Furthermore, carbachol was able to increase arrhythmia events and the beating frequency in BrS. CONCLUSION: Our hiPSC-CMs from a BrS-patient with two variants in SCN1B recapitulated some key phenotypic features of BrS and can provide a platform for studies on BrS with SCN1B variants

CO PROX over Pt-Sn/Al2O3: a combined kinetic and in situ DRIFTS study

SSCI-VIDE+ING+AMS:YSC:FRMInternational audiencePEM fuel-cell technology requires virtually CO-free hydrogen feedstocks. Preferential oxidation (PROX) aims at removing small amounts of CO in H2-rich streams by catalytic oxidation of CO at low temperatures, with minimal production of water. Bimetallic Pt-Sn catalysts have shown much higher activities for PROX than those based solely on Pt but the actual state of the active phase under reaction conditions is still a matter of debate. To further explore this issue, a combined DRIFTS (Diffuse Reflectance Infrared Fourier Transformed Spectroscopy) and kinetic study under similar CO PROX reaction conditions was performed on alumina-supported Pt-Sn and Pt exhibiting both well-controlled particle sizes

PROX reaction over Pt3Sn/Al2O3: Structural investigation by operando DRIFTS

International @ INGENIERIE+AMS:YSC:FRMInternational audiencePtxSn based catalysts have presented exhibit enhanced activities for preferential CO oxidation (PROX) as compared to analogous Pt catalysts. Yet, often ill-defined PtSn phases present on the catalyst prevent a full understanding of the reaction mechanism and active sites involved. Therefore we used for this study well-defined Pt and Pt3Sn catalysts, obtained by impregnation of pre-formed Pt or Pt3Sn nanoparticles [1]. Our 1% Pt3Sn/?-Al2O3 and 1% Pt/?-Al2O3 catalysts were used in the CO PROX. Experiments were carried out under controlled conditions to obtain intrinsic kinetics. Additionally an investigation of CO adsorption under the reaction mixture was carried out by operando DRIFTS over the samples. An unusual evolution of the adsorbed CO was noted while ramping up the temperature

Direct evidence of Pt-Sn alloy surface segregation at low temperatures by in situ IR of CO adsorption

National @ INGENIERIE+AMS:FRM:YSCInternational audienceIn the present study, a direct evidence of the surface segregation induced by CO adsorption on the structure of a Pt-Sn alloy supported on alumina is reported for the first time. The surface segregation was monitored by in situ diffuse reflectance FT-IR spectroscopy (DRIFTS) in a 2% CO/H2 atmosphere at various temperatures and showed to occur only below 175°C and was partly reversible following reduction at high temperature. The experiments are performed as well on a Sn-free sample for comparison and the behavior observed is typically to a Pt supported catalyst

Direct evidence of Pt-Sn alloy surface segregation at low temperatures by in situ IR of CO adsorption

National @ INGENIERIE+AMS:FRM:YSCInternational audienceIn the present study, a direct evidence of the surface segregation induced by CO adsorption on the structure of a Pt-Sn alloy supported on alumina is reported for the first time. The surface segregation was monitored by in situ diffuse reflectance FT-IR spectroscopy (DRIFTS) in a 2% CO/H2 atmosphere at various temperatures and showed to occur only below 175°C and was partly reversible following reduction at high temperature. The experiments are performed as well on a Sn-free sample for comparison and the behavior observed is typically to a Pt supported catalyst

CO PROX over Pt-Sn/Al2O3: A combined kinetic and in situ DRIFTS study

SSCI-VIDE+ING+AMS:FRM:YSCInternational audiencePreferential oxidation of CO (PROX) in hydrogen-rich mixtures was studied over alumina-supported Pt and Pt-Sn catalysts, which exhibited a well-defined metal particle size. The reaction rate was much faster over Pt-Sn/Al2O3 than over Pt/Al2O3. Significantly different apparent activation energies and oxygen reaction orders were found for both samples. Whereas the CO PROX kinetics over Pt/Al2O3 could be described by oxygen adsorption as being rate-determining step, this was not the case for Pt-Sn. In situ Diffuse Reflectance Infrared Fourier Transformed Spectroscopy (DRIFTS) showed that Pt-Sn, initially under a mixture of 1% CO/80% H-2, segregated upon the introduction of 2% O-2, even at temperatures where the alloy was stable under reducing conditions. For the CO PROX reaction over Pt-Sn/Al2O3 a bifunctional mechanism is proposed with CO and H being adsorbed on the platinum sites and oxygen being channeled from neighboring SnOx sites. This work suggests a Mars-Van Krevelen type of mechanism for the SnOx, site, in agreement with the low value of 0.2 for the oxygen reaction order over Pt-Sn. (C) 2015 Elsevier B.V. All rights reserved

DRIFTS of the PReferential OXidation of CO (PROX) over Pt-Sn/Al2O3: evidence of surface segregation under reaction conditions

SSCI-VIDE+ING+YSC:FRMInternational audienceNon

DRIFTS of the PReferential OXidation of CO (PROX) over Pt-Sn/Al2O3: evidence of surface segregation under reaction conditions

SSCI-VIDE+ING+YSC:FRMInternational audienceNon

Direct evidence by in situ IR CO monitoring of the formation and the surface segregation of a Pt-Sn alloy

INGENIERIE+AMS:YSC:FRMThe heat of CO adsorption on the Pt atoms of a Pt-Sn alloy phase could be specifically determined from in situ DRIFTS data and was found to be about half that measured on a plain Pt reference. Surprisingly, a reversible surface segregation of the Pt-Sn alloy was observed at temperatures below 175 degrees C

DRIFTS of the PReferential OXidation of CO (PROX) over Pt-Sn/Al2O3: evidence of surface segregation under reaction conditions

SSCI-VIDE+ING+YSC:FRMInternational audienceNon