State dependent dissociation of HERG channel inhibitors

BACKGROUND AND PURPOSE: Inhibition of HERG channels prolongs the ventricular action potential and the QT interval with the risk of torsade de pointes arrhythmias and sudden cardiac death. Many drugs induce greater inhibition of HERG channels when the cell membrane is depolarized frequently. The dependence of inhibition on the pulsing rate may yield different IC(50) values at different frequencies and thus affect the quantification of HERG channel block. We systematically compared the kinetics of HERG channel inhibition and recovery from block by 8 blockers at different frequencies. EXPERIMENTAL APPROACH: HERG channels were expressed heterologously in Xenopus oocytes and currents were measured with the two-electrode voltage clamp technique. KEY RESULTS: Frequency-dependent block was observed for amiodarone, cisapride, droperidol and haloperidol (group 1) whereas bepridil, domperidone, E-4031 and terfenadine (group 2) induced similar pulse-dependent block at all frequencies. With the group 1 compounds, HERG channels recovered from block in the presence of drug (recovery being voltage-dependent). No substantial recovery from block was observed with the second group of compounds. Washing out of bepridil, domperidone, E-4031 and terfenadine was substantially augmented by frequent pulsing. Mutation D540K in the HERG channel (which exhibits reopening at negative voltages) facilitated recovery from block by these compounds at −140 mV. CONCLUSION AND IMPLICATIONS: Drug molecules dissociate at different rates from open and closed HERG channels (‘use-dependent' dissociation). Our data suggest that apparently ‘trapped' drugs (group 2) dissociated from the open channel state whereas group 1 compounds dissociated from open and resting states

Electrical Resistivity Under Extreme Conditions In The Ce 3ir4sn13 Heavy Fermion Compound

We have performed measurements of temperature dependent electrical resistivity ρ(T) under pressures up to 27 kbar and down to 0.1 K on single crystals of the Ce3Ir4Sn13 heavy fermion compound. At ambient pressure (P=0) we have identified in the ρ(T) data interesting features associated with the presence of crystalline field effects, magnetic correlations, Kondo single impurity scattering and, possibly, a low temperature structural phase transition. All these features were mapped as a function of pressure which allowed us to construct a pressure-temperature phase diagram with these temperature scales. We have also carried out measurements of ρ(T) as a function of magnetic fields up to H=8 T and the important temperature scales in ρ(T) were followed with field. Enlightened also by temperature dependent specific heat experiments we discuss the possible microscopic origins of the features found in our ρ(T) data. © 2013 Elsevier Ltd.177132135Remeika, J.P., Espinosa, G.P., Cooper, A.S., Barz, H., Rowell, J.M., McWhan, D.B., Vandenberg, J.M., Thomlinson, W., (1980) Solid State Commun., 34, p. 923Hodeau, J.L., Chenavas, J., Marezio, M., Remeika, J.P., (1980) Solid State Commun., 36, p. 839Agüero, O., (2007), Ph.D. thesis, Universidade Estadual de Campinas, Campinas, SP, BrazilZhong, G., Lei, X., Mao, J., (2009) Phys. Rev. B, 79, p. 094424Sato, H., Fukuhara, T., Iwasaki, S., Aoki, Y., Sakamoto, I., Takayanagi, S., Wada, N., (1993) Physica B, 186-188, p. 630Prires, M.A., Mendonça Ferreira, L., Duque, J.G.S., Urbano, R.R., Agüero, O., Torriani, I., Rettori, C., Pagliuso, P.G., (2006) J. Appl. Phys., 99, pp. 08J311Mendonça Ferreira, L., Bittar, E.M., Pires, M.A., Urbano, R.R., Agüero, O., Torriani, I., Rettori, C., Baggio-Saitovich, E., (2006) Physica B, 384, p. 332Mardegan, J.R.L., Aliouane, N., Coelho, L.N., Agüero, O., Bittar, E.M., Lang, J.C., Pagliuso, P.G., Giles, C., (2013) IEEE Trans. Magn., 49, p. 4652Hundley, M.F., Sarrao, J.L., Thompson, J.D., Movshovich, R., Jaime, M., Petrovic, C., Fisk, Z., (2002) Phys. Rev. B, 65, p. 024401Ghosh, K., Ramakrishnan, S., Chandra, G., (1993) Phys. Rev. B, 48, p. 10435Klintberg, L.E., Goh, S.K., Alireza, P.L., Saines, P.J., Tompsett, D.A., Logg, P.W., Yang, J., Grosche, F.M., (2012) Phys. Rev. Lett., 109, p. 237008Israel, C., Bittar, E.M., Aguero, O.E., Urbano, R.R., Rettori, C., Torriani, I., Pagliuso, P.G., Borges, H.A., (2005) Physica B, 359-361, p. 251Thomas, E.L., Lee, H.-O., Bankston, A.N., Maquilon, S., Klavins, P., Maldovan, M., Young, D.P., Chan, J.Y., (2006) J. Solid State Chem., 179, p. 1642Köhler, U., Pikul, A., Oeschler, N., Westerkamp, T., Strydom, A.M., Steglich, F., (2007) J. Phys. Condens. Matter, 19, p. 386207Ślebarski, A., White, B.D., Fijałkowski, M., Goraus, J., Hamlin, J.J., Maple, M.B., (2012) Phys. Rev. B, 86, p. 205113Takayanagi, S., Sato, H., Fukuhara, T., Wada, N., (1994) Physica B, 199-200, p. 49Nagoshi, C., Sugawara, H., Aoki, Y., Sakai, S., Kohgi, M., Sato, H., Onimaru, T., Sakakibara, T., (2005) Physica B, 359-361, p. 248Canfield, P.C., Fisk, Z., (1992) Philos. Mag. B, 65, p. 1117Yang, C.P., Chen, Y.H., Wang, H., Nagoshi, C., Kohgi, M., Sato, H., (2008) Appl. Phys. Lett., 92, p. 092504Bittar, E.M., (2006), M.Sc. thesis, Universidade Estadual de Campinas, Campinas, SP, BrazilCornut, D., Coqblin, B., (1972) Phys. Rev. B, 5, p. 4541Stewart, G.R., (1984) Rev. Mod. Phys., 56, p. 755Continentino, M.A., (2005) Braz. J. Phys., 35, p. 197Löhneysen, H.V., Rosch, A., Vojta, M., Wölfle, P., (2007) Rev. Mod. Phys., 79, p. 1015Christianson, A.D., Bauer, E.D., Lawrence, J.M., Riseborough, P.S., Moreno, N.O., Pagliuso, P.G., Sarrao, J.L., McQueeney, R.J., (2004) Phys. Rev. B, 70, p. 134505Collave, J.R., in pressChristianson, A.D., Goremychkin, E.A., Gardner, J.S., Kang, H.J., Chung, J.-H., Manuel, P., Thompson, J.D., Lawrence, J.M., (2008) Physica B, 403, p. 909Cornelius, A.L., Christianson, A.D., Lawrence, J.L., Fritsch, V., Bauer, E.D., Sarrao, J.L., Thompson, J.D., Pagliuso, P.G., (2006) Physica B, 378-380, p. 113Pagliuso, P.G., Moreno, N.O., Curro, N.J., Thompson, J.D., Hundley, M.F., Sarrao, J.L., Fisk, Z., Cornelius, A.L., (2002) Phys. Rev. B, 66, p. 054433Light, B.E., Kumar, R.S., Cornelius, A.L., Pagliuso, P.G., Sarrao, J.L., (2004) Phys. Rev. B, 69, p. 02441

Pressure-temperature-composition Phase Diagram Of Ce2 Min8 ( M = Rh, Ir )

In this work a preliminary pressure-temperature-composition phase diagram for the Ce2 Rh( 1 - x ) Irx In8 heavy-fermions (HF) materials is reported, built from pressure-dependent electrical resistivity ( ρ ( T ) ) measurements on single-crystalline samples. Although neither of the two end members is an ambient-pressure SC, a transition to a zero-resistance (ZR) state was found at ambient pressure ( TC ≈ 600 mK ) in a narrow Ir concentration range (around x = 0.5). Pressures not higher than 10 kbar are sufficient to suppress this ZR state for all measured concentrations, in contrast to the 115 materials. © 2006 Elsevier B.V. All rights reserved.378-380SPEC. ISS.423425Hegger, H., (2000) Phys. Rev. Lett., 84, p. 4986Petrovic, C., (2001) J. Phys. Condens. Matter, 13, pp. L337Petrovic, C., (2001) Europhys. Lett., 53, p. 354Pagliuso, P.G., (2001) Phys. Rev. B, 64, pp. 100503RNicklas, M., (2004) Phys. Rev. B, 70, p. 020505Mathur, N.D., (1998) Nature, 394, p. 39Moreno, N.O., (2002) Physica B, 312-313, p. 274Morris, G.D., (2004) Phys. Rev. B, 69, p. 214415Chen, G.F., (2002) J. Phys. Soc. Japan, 71, p. 2836Bianchi, A., (2001) Phys. Rev. B, 64, pp. 220504RNicklas, M., (2003) Acta Phys. Pol. B, 34, p. 90

Pressure-temperature Phase Diagrams Of In-plane Doped Cerhin5

In this work, we report a combined study about the effects of pressure and in-plane doping on the low temperature properties of AFM CeRhIn5. We have explored two different kinds of in-plane doping to perturb the AFM state of CeRhIn5. The La-doping in the Ce-site, which suppresses the AFM order simply by dilution and the Sn-doping in the In-sites, that suppresses the AFM order by increasing the Kondo-coupling. Electrical resistivity measurements under pressure were performed and the extracted pressure-temperature diagrams for these in-plane perturbed CeRhIn5 single crystals are compared to the properties of the pure compound. © 2007 Elsevier B.V. All rights reserved.460-462 ISPEC. ISS.672673Hegger, H., (2000) Phys. Rev. Lett., 84, p. 4986Pagliuso, P.G., (2001) Phys. Rev. B, 64, p. 100503. , (R)Petrovic, C., (2001) J. Phys.: Condens. Mat., 13, pp. L337Petrovic, C., (2001) Europhys. Lett., 53, p. 54Park, T., (2006) Nature, 440, p. 65Daniel, M., (2005) Phys. Rev. Lett., 95, p. 016406Fisher, R.A., (2002) Phys. Rev. B., 65, p. 22450

Two Superconducting Phases In The Bi-layered Alloys Ce2 Rh1 - X Irx In8

We report pressure and temperature dependent electrical resistivity measurements in the Ce2 Rh1 - x Irx In8 alloys. Our results revealed two phases with zero resistance. One of these phases is induced by pressure, occurring for a range of compositions situated near the Rh-rich extreme, consistent with the behavior observed for the pure Ce2 RhIn8 compound. The second transition occurs for intermediate concentrations (x ∼ 0.5 - 0.7), and in sharp contrast with the first transition, is progressively eliminated by the application of pressure. We compare the findings in the Ce2 Rh1 - x Irx In8 alloys to its related CeRh1 - x Irx In5, discussing how the occurrence of the superconducting phases may become unfavorable for the bi-layer alloys due to higher dimensionality and stronger disorder. © 2007 Elsevier B.V. All rights reserved.4035-9780782Thompson, J.D., (2001) J. Magn. Magn. Mater., 226-230, p. 5Hegger, H., (2000) Phys. Rev. Lett., 84, p. 4986Mathur, N., (1998) Nature, 394, p. 39Mito, T., (2001) Phys. Rev. B, 63, pp. 220507RPagliuso, P.G., (2001) Phys. Rev. B, 64, pp. 100503RPagliuso, P.G., (2002) Physica B, 312-313, p. 129Pham, L.D., (2006) Phys. Rev. Lett., 97, p. 056404Zheng, G.Q., (2004) Phys. Rev. B, 70, p. 014511Nicklas, M., (2003) Phys. Rev. B, 67, pp. 020506RChen, G.F., (2002) J. Phys. Soc. Japan, 71, p. 2836Morris, G.D., (2004) Phys. Rev. B, 69, p. 214415Nicklas, M., (2004) Phys. Rev. B, 70, pp. 020505RMoshopoulou, E.G., (2001) J. Solid State Chem., 158, p. 25Moshopoulou, E.G., (2006) Acta Crystallogr. B, 62, p. 17

Tuning The Pressure-induced Superconducting Phase In Doped Cerhin5

Pressure- and temperature-dependent heat capacity and electrical resistivity experiments on Sn- and La-doped CeRhIn5 are reported for two samples with specific concentrations, Ce0.90La0.10RhIn5 and CeRhIn4.84Sn0.16, which present the same TN=2.8K. The obtained P-T phase diagrams for doped CeRhIn5 compared to that for the pure compound show that Sn doping shifts the diagram to lower pressures while La doping does exactly the opposite, indicating that the important energy scale to define the pressure range for superconductivity in CeRhIn5 is the strength of the on-site Kondo coupling. © 2008 The American Physical Society.1011Continentino, M.A., (2005) Braz. J. Phys., 35, p. 197. , BJPHE6 0103-9733 10.1590/S0103-97332005000100018Pagliuso, P.G., (2001) Phys. Rev. B, 64, pp. 100503R. , PRBMDO 0163-1829 10.1103/PhysRevB.64.100503Pagliuso, P.G., (2002) Physica (Amsterdam), 312B-313B, p. 129. , PHYBE3 0921-4526 10.1016/S0921-4526(01)01281-9Pham, L.D., (2006) Phys. Rev. Lett., 97, p. 056404. , PRLTAO 0031-9007 10.1103/PhysRevLett.97.056404Zapf, V.S., (2001) Phys. Rev. B, 65, p. 014506. , PRBMDO 0163-1829 10.1103/PhysRevB.65.014506Park, T., (2006) Nature (London), 440, p. 65. , NATUAS 0028-0836 10.1038/nature04571Hegger, H., (2000) Phys. Rev. Lett., 84, p. 4986. , PRLTAO 0031-9007 10.1103/PhysRevLett.84.4986Mito, T., (2001) Phys. Rev. B, 63, pp. 220507R. , PRBMDO 0163-1829 10.1103/PhysRevB.63.220507Nicklas, M., (2004) Phys. Rev. B, 70, pp. 020505R. , PRBMDO 0163-1829 10.1103/PhysRevB.70.020505Petrovic, C., (2001) J. Phys. Condens. Matter, 13, p. 337. , JCOMEL 0953-8984 10.1088/0953-8984/13/17/103Petrovic, C., (2001) Europhys. Lett., 53, p. 354. , EULEEJ 0295-5075 10.1209/epl/i2001-00161-8Urbano, R.R., (2007) Phys. Rev. Lett., 99, p. 146402. , PRLTAO 0031-9007 10.1103/PhysRevLett.99.146402Zheng, G., (2004) Phys. Rev. B, 70, p. 014511. , PRBMDO 0163-1829 10.1103/PhysRevB.70.014511Pagliuso, P.G., (2002) Phys. Rev. B, 66, p. 054433. , PRBMDO 0163-1829 10.1103/PhysRevB.66.054433Bauer, E.D., (2006) Physica (Amsterdam), 378B-380B, p. 142. , PHYBE3 0921-4526 10.1016/j.physb.2006.01.053Daniel, M., (2005) Phys. Rev. Lett., 95, p. 016406. , PRLTAO 0031-9007 10.1103/PhysRevLett.95.016406Ramos, S.M., (2005) Physica (Amsterdam), 359B-361B, p. 398. , PHYBE3 0921-4526 10.1016/j.physb.2005.01.076Ramos, S.M., (2007), Ph.D. thesis, UFF, BrazilPetrovic, C., (2002) Phys. Rev. B, 66, p. 054534. , PRBMDO 0163-1829 10.1103/PhysRevB.66.054534Christianson, A.D., (2002) Phys. Rev. B, 66, p. 054410. , PRBMDO 0163-1829 10.1103/PhysRevB.66.054410Werthamer, N.R., (1966) Phys. Rev., 147, p. 295. , PHRVAO 0031-899X 10.1103/PhysRev.147.295Kumar, R.S., (2004) Phys. Rev. B, 69, p. 014515. , PRBMDO 0163-1829 10.1103/PhysRevB.69.014515Bauer, E.D., (2006) Phys. Rev. B, 73, p. 245109. , PRBMDO 0163-1829 10.1103/PhysRevB.73.245109Donath, J.G., (2007) Physica (Amsterdam), 460C-462C, p. 661. , PHYCE6 0921-4534 10.1016/j.physc.2007.03.030Nicklas, M., (2001) J. Phys. Condens. Matter, 13, p. 905. , JCOMEL 0953-8984 10.1088/0953-8984/13/44/104Shishido, H., (2005) J. Phys. Soc. Jpn., 74, p. 1103. , JUPSAU 0031-9015 10.1143/JPSJ.74.110