Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito
Abstract
The Ca 2+-independent transient outward K+ current ( I to) plays an important electrophysiological role in normal and diseased hearts. However, its contribution to ventricular repolarization remains controversial because of differences in its phenotypic expression and function across species. The dog, a frequently used model of human cardiac disease, exhibits altered functional expression of I to. To better understand the relevance of electrical remodeling in dogs to humans, we studied the phenotypic differences in ventricular I to of both species with electrophysiological, pharmacological, and protein-chemical techniques. Several notable distinctions were elucidated, including slower current decay, more rapid recovery from inactivation, and a depolarizing shift of steady-state inactivation in human vs. canine I to. Whereas recovery from inactivation of human I to followed a monoexponential time course, canine I to recovered with biexponential kinetics. Pharmacological sensitivity to flecainide was markedly greater in human than canine I to, and exposure to oxidative stress did not alter the inactivation kinetics of I to in either species. Western blot analysis revealed immunoreactive bands specific for Kv4.3, Kv1.4, and Kv channel-interacting protein (KChIP)2 in dog and human, but with notable differences in band sizes across species. We report for the first time major variations in phenotypic properties of human and canine ventricular I to despite the presence of the same subunit proteins in both species. These data suggest that differences in electrophysiological and pharmacological properties of I to between humans and dogs are not caused by differential expression of the K channel subunit genes thought to encode I to, but rather may arise from differences in molecular structure and/or posttranslational modification of these subunits.
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Despite high similarity between human and canine myocardium, some differences have been reported, including resting and exercise heart rates, kinetics of Ito current inactivation, its recovery, molecular size of corresponding ion channels, sensitivity to flecanide, and transmural epicardial:endocardial expression levels of HERG ion channel.
“Such differences include resting and exercise heart rates (see above), kinetics of Ito current inactivation, its recovery, and molecular size of its corresponding ion channels, sensitivity to flecanide (Akar, et al., 2004), and transmural epicardial:endocardial expression levels of HERG ion channel (Szabo, et al., 2005).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Akar, et al., 2004
Cites
Yan, G., & Antzelevitch, C. (1999) · Circulation · doi:10.1161/01.cir.100.15.1660 · Cited by 1,132 · see citing works
Modulation of A-type potassium channels by a family of calcium sensors
An, W., Bowlby, M. R., Betty, M., Cao, J., Ling, H., Mendoza, G., Hinson, J., Mattsson, K. I., Strassle, B. W., Trimmer, J. S., et al. (2000) · Nature · doi:10.1038/35000592 · Cited by 959 · see citing works
Winslow, R. L., Rice, J. J., Jafri, S., Marbán, E., & O'Rourke, B. P. (1999) · Circulation Research · doi:10.1161/01.res.84.5.571 · Cited by 797 · see citing works
Beuckelmann, D. J., Näbauer, M., & Erdmann, E. (1993) · Circulation Research · doi:10.1161/01.res.73.2.379 · Cited by 736 · see citing works
Kääb, S., Nuss, H. B., Chiamvimonvat, N., O'Rourke, B. P., Pak, P. H., Kass, D. A., Marbán, E., & Tomaselli, G. F. (1996) · Circulation Research · doi:10.1161/01.res.78.2.262 · Cited by 572 · see citing works
Self-citationTransient outward current prominent in canine ventricular epicardium but not endocardium.
Litovsky, S. H., & Antzelevitch, C. N. (1988) · Circulation Research · doi:10.1161/01.res.62.1.116 · Cited by 436 · see citing works
The Brugada Syndrome: Ionic Basis and Arrhythmia Mechanisms
Antzelevitch, C. (2001) · Journal of Cardiovascular Electrophysiology · doi:10.1046/j.1540-8167.2001.00268.x · Cited by 415 · see citing works
Molecular Basis of Transient Outward Potassium Current Downregulation in Human Heart Failure
Kääb, S., Dixon, J., Duc, J., Ashen, M. D., Näbauer, M., Beuckelmann, D. J., Steinbeck, G., McKinnon, D. H., & Tomaselli, G. F. (1998) · Circulation · doi:10.1161/01.cir.98.14.1383 · Cited by 401 · see citing works
Self-citationIonic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males
Diego, J. M. D., Cordeiro, J. M., Goodrow, R. J., Fish, J. M., Zygmunt, A. C., Pérez, G. J., Scornik, F. S., & Antzelevitch, C. N. (2002) · Circulation · doi:10.1161/01.cir.0000032002.22105.7a · Cited by 393 · see citing works
Mechanisms of Altered Excitation-Contraction Coupling in Canine Tachycardia-Induced Heart Failure, I
O'Rourke, B. P., Kass, D. A., Tomaselli, G. F., Kääb, S., Tunin, R. S., & Marbán, E. (1999) · Circulation Research · doi:10.1161/01.res.84.5.562 · Cited by 341 · see citing works
Self-citationRosati, B., Pan, Z., Lypen, S., Wang, H., Cohen, I. S., Dixon, J. E., & McKinnon, D. H. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0119b.x · Cited by 279 · see citing works
Lukas, A., & Antzelevitch, C. (1993) · Circulation · doi:10.1161/01.cir.88.6.2903 · Cited by 277 · see citing works
Hobai, I. A., & O'Rourke, B. P. (2001) · Circulation · doi:10.1161/01.cir.103.11.1577 · Cited by 266 · see citing works
Transmural action potential and ionic current remodeling in ventricles of failing canine hearts
Li, G., Lau, C., Ducharme, A., Tardif, J., & Nattel, S. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00105.2002 · Cited by 245 · see citing works
Flecainide-induced arrhythmia in canine ventricular epicardium. Phase 2 reentry?
Krishnan, S., & Antzelevitch, C. (1993) · Circulation · doi:10.1161/01.cir.87.2.562 · Cited by 242 · see citing works
Näbauer, M., Beuckelmann, D. J., & Erdmann, E. (1993) · Circulation Research · doi:10.1161/01.res.73.2.386 · Cited by 236 · see citing works
Two components of transient outward current in canine ventricular myocytes.
Tseng, G., & Hoffman, B. F. (1989) · Circulation Research · doi:10.1161/01.res.64.4.633 · Cited by 220 · see citing works
Greenstein, J. L., Wu, R., Po, S. S., Tomaselli, G. F., & Winslow, R. L. (2000) · Circulation Research · doi:10.1161/01.res.87.11.1026 · Cited by 213 · see citing works
Self-citationWang, Z., Feng, J., Shi, H., Pond, A. L., Nerbonne, J. M., & Nattel, S. (1999) · Circulation Research · doi:10.1161/01.res.84.5.551 · Cited by 199 · see citing works
Shibata, R., Nakahira, K., Shibasaki, K., Wakazono, Y., Imoto, K., & Ikenaka, K. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04145.2000 · Cited by 175 · see citing works
Cellular basis of ventricular arrhythmias and abnormal automaticity in heart failure
Nuss, H. B., Kääb, S., Kass, D. A., Tomaselli, G. F., & Marbán, E. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.1.h80 · Cited by 174 · see citing works
Self-citationModulation of Kv4.3 current by accessory subunits
Deschênes, I., & Tomaselli, G. F. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03296-9 · Cited by 167 · see citing works
Self-citationIsoform-Specific Modulation of Voltage-Gated Na + Channels by Calmodulin
Deschênes, I., Neyroud, N., DiSilvestre, D. A., Marbán, E., Yue, D. T., & Tomaselli, G. F. (2002) · Circulation Research · doi:10.1161/01.res.0000012502.92751.e6 · Cited by 152 · see citing works
Self-citationWickenden, A. D., Kaprielian, R., Parker, T. G., Jones, O., & Backx, P. H. (1997) · The Journal of Physiology · doi:10.1111/j.1469-7793.1997.271be.x · Cited by 151 · see citing works
Slawsky, M., & Castle, N. A. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38711-2 · Cited by 138 · see citing works
Cloning and Expression of a Novel K+ Channel Regulatory Protein, KChAP
Wible, B. A., Yang, Q., Kuryshev, Y. A., Accili, E. A., & Brown, A. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.19.11745 · Cited by 121 · see citing works
Regulation of Kv4.3 Current by KChIP2 Splice Variants
Deschênes, I., DiSilvestre, D. A., Juang, G., Wu, R. C. H., An, W., & Tomaselli, G. F. (2002) · Circulation · doi:10.1161/01.cir.0000025417.65658.b6 · Cited by 117 · see citing works
Self-citationRegional contributions ofKv1.4,Kv4.2, andKv4.3to transient outward K+current in rat ventricle
Wickenden, A. D., Jegla, T. J., Kaprielian, R., & Backx, P. H. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.276.5.h1599 · Cited by 114 · see citing works
Molecular Remodeling of Kv4.3 Potassium Channels in Human Atrial Fibrillation
Grammer, J. B., BOSCH, R. F., Kühlkamp, V., & Seipel, L. (2000) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2000.tb00024.x · Cited by 103 · see citing works
Yeola, S. N., & Snyders, D. J. (1997) · Cardiovascular Research · doi:10.1016/s0008-6363(96)00221-0 · Cited by 103 · see citing works
KChAP as a chaperone for specific K+channels
Kuryshev, Y. A., Gudz, T. I., Brown, A. M., & Wible, B. A. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.278.5.c931 · Cited by 100 · see citing works
Kvβ Subunits Increase Expression of Kv4.3 Channels by Interacting with Their C Termini
Yang, E.-K., Alvira, M. R., Levitan, E. S., & Takimoto, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m004768200 · Cited by 92 · see citing works
Decher, N. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00374-1 · Cited by 87 · see citing works
Kong, W., Po, S. S., Yamagishi, T., Ashen, M. D., Stetten, G., & Tomaselli, G. F. (1998) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1998.275.6.h1963 · Cited by 82 · see citing works
Self-citationRolf, S., Haverkamp, W., Borggrefe, M., Mußhoff, U., Eckardt, L., Mergenthaler, J., Snyders, D. J., Pongs, O., Speckmann, E., Breithardt, G., et al. (2000) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s002100000257 · Cited by 81 · see citing works
Elucidating KChiP effects on Kv4.3 inactivation and recovery kinetics with a minimal KChiP2 isoform
Patel, S. P., Campbell, D. L., & Strauss, H. C. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.031856 · Cited by 76 · see citing works
Nerbonne, J. M., & Guo, W. (2002) · Journal of Cardiovascular Electrophysiology · doi:10.1046/j.1540-8167.2002.00406.x · Cited by 74 · see citing works
Petersen, K. R., & Nerbonne, J. M. (1999) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240050792 · Cited by 67 · see citing works
Zhu, X. R., Wulf, A., Schwarz, M., Isbrandt, D., & Pongs, O. (1999) · PubMed · Cited by 66 · see citing works
KChAP/Kvβ1.2 interactions and their effects on cardiac Kv channel expression
Kuryshev, Y. A., Wible, B. A., Gudz, T. I., Ramirez, A. N., & Brown, A. M. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.281.1.c290 · Cited by 65 · see citing works
Block of transient outward-type cloned cardiac K+ channel currents by quinidine.
Yatani, A., Wakamori, M., Mikala, G., & Bahinski, A. (1993) · Circulation Research · doi:10.1161/01.res.73.2.351 · Cited by 50 · see citing works
Protection of ischemic hearts by high glucose is mediated, in part, by GLUT-4
Ramasamy, R., Hwang, Y. C., Whang, J., & Bergmann, S. R. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.281.1.h290 · Cited by 50 · see citing works
A comparison of transient outward currents in canine cardiac Purkinje cells and ventricular myocytes
Han, W., Wang, Z., & Nattel, S. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.279.2.h466 · Cited by 50 · see citing works
Quinidine Interactions With Human Atrial Potassium Channels
Nenov, N. I., Crumb, W., Pigott, J. D., Harrison, L. H., & Clarkson, C. W. (1998) · Circulation Research · doi:10.1161/01.res.83.12.1224 · Cited by 29 · see citing works
Tseng, G. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(98)00282-x · Cited by 24 · see citing works
Abriel, H., Motoike, H. K., & Kass, R. S. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.278.5.c863 · Cited by 10 · see citing works
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O'Hara, T., Virág, L., Varró, A., & Rudy, Y. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002061 · Cited by 1,196 · see citing works
Molecular Physiology of Cardiac Repolarization
Nerbonne, J. M., & Kass, R. S. (2005) · Physiological Reviews · doi:10.1152/physrev.00002.2005 · Cited by 1,054 · see citing works
Calløe, K. (2019) · Acta Physiologica · doi:10.1111/apha.13225 · Cited by 993 · see citing works
Small and large animal models in cardiac contraction research: advantages and disadvantages
Milani-Nejad, N., & Janssen, P. M. L. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.007 · Cited by 484 · see citing works
Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy
Akar, F. G., SPRAGG, D. D., Tunin, R. S., Kass, D. A., & Tomaselli, G. F. (2004) · Circulation Research · doi:10.1161/01.res.0000144125.61927.1c · Cited by 308 · see citing works
Self-citationSodium current deficit and arrhythmogenesis in a murine model of plakophilin-2 haploinsufficiency
Cerrone, M., Noorman, M., Lin, X., Chkourko, H., Liang, F., van der Nagel, R., Hund, T. J., Birchmeier, W., Mohler, P. J., van Veen, T. A. B., et al. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs218 · Cited by 216 · see citing works
Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome
Wolpert, C., Echternach, C., Veltmann, C., Antzelevitch, C. N., Thomas, G. P., SPEHL, S., Streitner, F., Kuschyk, J., Schimpf, R., Haase, K. K., et al. (2005) · Heart Rhythm · doi:10.1016/j.hrthm.2004.11.025 · Cited by 192 · see citing works
Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium
SZENTADRASSY, N., BANYASZ, T., BIRO, T., SZABO, G., TOTH, B., MAGYAR, J., LAZAR, J., VARRO, A., KOVACS, L., & NANASI, P. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.11.022 · Cited by 185 · see citing works
Szabó, G., Szentandrássy, N., Bíró, T., Tóth, B. I., Czifra, G., Magyar, J., Bányász, T., Varró, A., Kovács, L., & Nánási, P. P. (2005) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-005-1445-z · Cited by 134 · see citing works
O’Hara, T., & Rudy, Y. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00785.2011 · Cited by 131 · see citing works
Mechanisms of Disease: ion channel remodeling in the failing ventricle
Nass, R. D., Aiba, T., Tomaselli, G. F., & Akar, F. G. (2008) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio1130 · Cited by 98 · see citing works
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Xiao, L., Koopmann, T. T., Ördög, B., Postema, P. G., Verkerk, A. O., Iyer, V., Sampson, K. J., Boink, G. J. J., Mamarbachi, M., Varró, A., et al. (2013) · Circulation Research · doi:10.1161/circresaha.112.300227 · Cited by 96 · see citing works
El-Haou, S., Balse, E., Neyroud, N., Dilanian, G., Gavillet, B., Abriel, H., Coulombe, A., Jeromin, A., & Hatem, S. N. (2009) · Circulation Research · doi:10.1161/circresaha.108.191007 · Cited by 92 · see citing works
Akar, F. G., Wu, R. C. H., Juang, G., Tian, Y., Burysek, M., DiSilvestre, D. A., Xiong, W., Armoundas, A. A., & Tomaselli, G. F. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00320.2004 · Cited by 84 · see citing works
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Rota, M., Hosoda, T., De Angelis, A., Arcarese, M. L., Esposito, G., Rizzi, R., Tillmanns, J., Tugal, D., Musso, E., Rimoldi, O., et al. (2007) · Circulation Research · doi:10.1161/circresaha.107.151449 · Cited by 75 · see citing works
Computational approaches to understand cardiac electrophysiology and arrhythmias
Roberts, B. N., Yang, P., Vaughn‐Behrens, S. B., Moreno, J. D., & Clancy, C. E. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01081.2011 · Cited by 75 · see citing works
Species-Dependent Mechanisms of Cardiac Arrhythmia: A Cellular Focus
Edwards, A. G., & Louch, W. E. (2017) · Clinical Medicine Insights Cardiology · doi:10.1177/1179546816686061 · Cited by 74 · see citing works
Cordeiro, J. M., Nesterenko, V. V., Sicouri, S., Goodrow, R. J., Treat, J. A., Desai, M., Wu, Y., Doss, M. X., Antzelevitch, C. N., & Diego, J. M. D. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.03.014 · Cited by 65 · see citing works
Pekkanen-Mattila, M., Chapman, H., Kerkelä, E., Suuronen, R., Skottman, H., Koivisto, A., & Aalto‐Setälä, K. (2010) · Experimental Biology and Medicine · doi:10.1258/ebm.2010.009345 · Cited by 64 · see citing works
Stokoe, K. S., Balasubramaniam, R., Goddard, C. A., Colledge, W. H., Grace, A. A., & Huang, C. L.-H. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.128785 · Cited by 60 · see citing works
Calløe, K., Soltysinska, E., Jespersen, T., Lundby, A., Antzelevitch, C. N., Olesen, S., & Cordeiro, J. M. (2009) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.07.017 · Cited by 50 · see citing works
Effect of the Itoactivator NS5806 on cloned Kv4 channels depends on the accessory protein KChIP2
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Aromolaran, A. S., & Boutjdir, M. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00431 · Cited by 44 · see citing works
Regulation of ion channels and arrhythmias in the ischemic heart
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Self-citationJohnson, E. K., Springer, S. J., Wang, W., Dranoff, E. J., Zhang, Y., Kanter, E. M., Yamada, K. A., & Nerbonne, J. M. (2018) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.117.005914 · Cited by 42 · see citing works
Liu, X., Qu, C., Yang, H., Shi, S., Zhang, C., Zhang, Y., Liang, J., & Yang, B. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00607.2017 · Cited by 42 · see citing works
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Taggart, P. I., Orini, M., Hanson, B. M., Hayward, M. P., Clayton, R. H., Dobrzynski, H., Yanni, J., Boyett, M. R., & Lambiase, P. D. (2014) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2014.06.004 · Cited by 36 · see citing works
Calløe, K., Nof, E., Jespersen, T., Diego, J. M. D., Chlus, N., Olesen, S., Antzelevitch, C. N., & Cordeiro, J. M. (2011) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2011.02053.x · Cited by 33 · see citing works
Properties and Molecular Determinants of the Natural Flavone Acacetin for Blocking hKv4.3 Channels
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Nánási, P. P., Horváth, B., Tar, F., Almássy, J., Szentandrássy, N., Jost, N., Baczkó, I., Bányász, T., & Varró, A. (2021) · Pharmaceuticals · doi:10.3390/ph14080748 · Cited by 25 · see citing works
Zang, Y., Dai, L., Zhan, H., Dou, J., Xia, L., & Zhang, H. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2012.11.020 · Cited by 25 · see citing works
Zhang, Y., Wu, W., Sun, H., Deng, X., Cheng, L., Li, X., Tse, H., Lau, C., & Li, G. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr347 · Cited by 25 · see citing works
Long, V. P., Bonilla, I. M., Vargas-Pinto, P. A., Nishijima, Y., Sridhar, A., Li, C., Mowrey, K. A., Wright, P., Velayutham, M., Kumar, S., et al. (2015) · Life Sciences · doi:10.1016/j.lfs.2014.12.024 · Cited by 24 · see citing works
Ni, H., Zhang, H., Grandi, E., Narayan, S. M., & Giles, W. R. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00251.2018 · Cited by 24 · see citing works
Vecchietti, S., Grandi, E., Severi, S., Rivolta, I., Napolitano, C., Priori, S. G., & Cavalcanti, S. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00270.2006 · Cited by 23 · see citing works
Hsiao, C.-T., Tropea, T. F., Fu, S.-J., Bardakjian, T., Gonzalez‐Alegre, P., Soong, B., Tang, C., & Jeng, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158247 · Cited by 22 · see citing works
Anti-arrhythmic properties of non-antiarrhythmic medications
Williams, E. A., Russo, V., Ceraso, S., Gupta, D., & Barrett‐Jolley, R. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104762 · Cited by 20 · see citing works
Tan, X., Cheng, X., Zhang, L., Wu, B., Liu, Q., Meng, J., Xu, H., & Cao, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101545 · Cited by 19 · see citing works
Cheng, H., Cannell, M. B., & Hancox, J. C. (2017) · Physiological Reports · doi:10.14814/phy2.13172 · Cited by 17 · see citing works
Abi‐Gerges, N., Miller, P. E., & Ghetti, A. (2019) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201021666191210142023 · Cited by 18 · see citing works
Wang, L., Sun, L., Zhang, Y., Hui-wei, W., Li, C., Pan, Z., Lu, Y., & Yang, B. (2009) · Cellular Physiology and Biochemistry · doi:10.1159/000218177 · Cited by 18 · see citing works
Kurokawa, S., Niwano, S., Niwano, H., Murakami, M., Ishikawa, S., Masaki, Y., Tamaki, H., Toda, T., Noda, Y., Shimizu, T., et al. (2014) · Circulation Journal · doi:10.1253/circj.cj-13-1587 · Cited by 17 · see citing works
Tur, J., Chapalamadugu, K. C., Katnik, C. P., Cuevas, J., Bhatnagar, A., & Tipparaju, S. M. (2016) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00281.2016 · Cited by 17 · see citing works
Nagy, N., Szél, T., Jost, N., Tóth, A., Papp, J. G., & Varró, A. (2015) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2014-0532 · Cited by 15 · see citing works
Allicin inhibits transient outward potassium currents in mouse ventricular myocytes
CAO, H., Huang, C., & WANG, X. (2016) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2016.3116 · Cited by 15 · see citing works
Treat, J. A., Goodrow, R. J., Bot, C. T., Haedo, R. J., & Cordeiro, J. M. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.08.010 · Cited by 14 · see citing works
Zhang, H., Zhang, H., Wang, C., Wang, Y., Zou, R., Shi, C., Guan, B., Gamper, N. L., & Xu, Y. (2019) · The FASEB Journal · doi:10.1096/fj.201902010rr · Cited by 13 · see citing works
Cordeiro, J. M., Pérez, G. J., Schmitt, N., Pfeiffer, R. D., Nesterenko, V. V., Burashnikov, E., Veltmann, C., Borggrefe, M. M., Wolpert, C., Schimpf, R., et al. (2010) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y10-094 · Cited by 13 · see citing works
Ehrlich, J. R., Hoche, C., Coutu, P., Metz-Weidmann, C., Dittrich, W., Hohnloser, S. H., Nattel, S., & Gögelein, H. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.110080 · Cited by 13 · see citing works
Liu, X., Shi, S., Yang, H., Qu, C., Chen, Y., Liang, J., & Yang, B. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00092.2017 · Cited by 12 · see citing works
Solth, A., Siebrands, C. C., & Friederich, P. (2005) · Anesthesiology · doi:10.1097/00000542-200510000-00018 · Cited by 12 · see citing works
Wang, N., Dries, E., Fowler, E. D., Harmer, S. C., Hancox, J. C., & Cannell, M. B. (2021) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2021.11.004 · Cited by 10 · see citing works
Kv4.2 and KChIP2 transcription in individual cardiomyocytes from the rat left ventricular free wall
Schultz, J., JANZEN, C., Volk, T. J., & Ehmke, H. (2005) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2005.02.025 · Cited by 10 · see citing works
Fan, Y. (2015) · Medical Science Monitor · doi:10.12659/msm.893414 · Cited by 8 · see citing works
A General Model of Ion Passive Transmembrane Transport Based on Ionic Concentration
Wang, V. Q., & Liu, S. (2019) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2018.00110 · Cited by 8 · see citing works
Cardiac contractility modulation in patients with heart failure — A review of the literature
Bazoukis, G., Saplaouras, A., Efthymiou, P., Yiannikourides, A., Liu, T., Letsas, Κ. P., Efremidis, M., Lampropoulos, K. M., Xydonas, S., Tse, G., et al. (2024) · Heart Failure Reviews · doi:10.1007/s10741-024-10390-1 · Cited by 7 · see citing works
Self-citationZhang, R., Jie, L., Wu, W., Wang, Z., Sun, H., Xiao, G.-S., Wang, Y., Li, Y., & Li, G. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.03.029 · Cited by 7 · see citing works
Fowler, E. D., Wang, N., Hezzell, M., Chanoit, G. P. A., Hancox, J. C., & Cannell, M. B. (2022) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2022.07.009 · Cited by 6 · see citing works
Hyperkaliémie sévère ou menaçante : le diable est dans les détails
Robert, T., Algalarrondo, V., & Mesnard, L. (2015) · Réanimation · doi:10.1007/s13546-015-1125-8 · Cited by 6 · see citing works
Animal Models of Disease for Future Toxicity Predictions
Morgan, S. J., & Elangbam, C. S. (2016) · doi:10.1002/9781119053248.ch18 · Cited by 5 · see citing works
Using induced pluripotent stem cells for drug discovery in arrhythmias
Teles, D., & Fine, B. M. (2024) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2024.2360420 · Cited by 4 · see citing works
Electrophysiological Remodeling in Heart Failure
Akar, F. G., & Tomaselli, G. F. (2013) · Springer eBooks · doi:10.1007/978-1-4471-4881-4_22 · Cited by 3 · see citing works
Self-citationMolecular Physiology of Ion Channels That Control Cardiac Repolarization
Nerbonne, J. M., & Kass, R. S. (2007) · Humana Press eBooks · doi:10.1007/978-1-59259-884-7_2 · Cited by 2 · see citing works
Jost, N., Muntean, D. M., & Christ, T. (2015) · Springer eBooks · doi:10.1007/978-3-319-15961-4_46 · Cited by 2 · see citing works
Jin, Q., Greenstein, J. L., & Winslow, R. L. (2022) · Biophysical Journal · doi:10.1016/j.bpj.2021.11.2262 · Cited by 2 · see citing works
Inhibition of Cardiac Kv4.3/KChIP2 Channels by Sulfonylurea Drug Gliquidone
Yang, C., Li, Q., Hu, F., Liu, Y., & Wang, K. (2023) · Molecular Pharmacology · doi:10.1124/molpharm.123.000787 · Cited by 2 · see citing works
Human Stem‐Cell‐Derived Cardiomyocytes in Drug Discovery and Toxicity Testing
Szebényi, K., Péntek, A., Varga, N., Erdei, Z., Vőfély, G., Orbán, T. I., Sarkadi, B., & Apáti, Á. (2014) · doi:10.1002/9781118856017.ch15 · Cited by 2 · see citing works
Basic Physiology of Ion Channel Function
Baró, I., & Escande, D. (2008) · Springer eBooks · doi:10.1007/978-1-84628-854-8_2 · Cited by 1 · see citing works
Ding, H., Yang, X., Liu, X., Liu, T.-F., & Bao, R.-F. (2006) · PubMed · Cited by 1 · see citing works
Composition and function of ion channels and their effects on cardiac remodeling
Duttaroy, A. K., & Mallick, R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99570-2.00006-0 · Cited by 1 · see citing works
O’Hara, T. (2011) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k70r9mcm · Cited by 1 · see citing works
Electrophysiological remodeling in Dilated Cardiomyopathy and Heart Failure
Akar, F. G., & Tomaselli, G. F. (2008) · Springer eBooks · doi:10.1007/978-1-84628-854-8_19 · Cited by 1 · see citing works
Self-citationLarge Animal Models for Cardiac Cell Therapy
Migliati, E. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801888-0.00003-5 · Cited by 1 · see citing works
Hormonal Control of Cardiac Action Potential Phase 1 Currents in the Brugada Syndrome
Argenziano, M., Tiscornia, G., Moretta, R., Amorena, C. E., & Gras, E. G. (2014) · Revista Argentina de Cardiología · doi:10.7775/rac.v82.i4.3885
Tsuji, Y., Harrell, D. T., Ishikawa, T., & Makita, N. (2015) · Japanese Journal of Electrocardiology · doi:10.5105/jse.35.104
The Role Of Homeodomain Transcription Factor Irx5 In Cardiac Contractility and Hypertrophic Response
Kim, K. H. (2012) · TSpace (University of Toronto)
Role of ion channels in human induced pluripotent stem cells–derived cardiomyocytes
Treat, J. A., Jankova, M., Calløe, K., & Cordeiro, J. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-90059-1.00001-4
Basic Physiology of Ion Channel Function
Baró, I., Escande, D., & Demolombe, S. (2013) · Springer eBooks · doi:10.1007/978-1-4471-4881-4_2
Beyond GDMT: bridging the therapeutic gap in heart failure
Letarte, L., Raje, V., Feliberti, J. P., Antoine, S., Bindra, A. S., YARANOV, D. M., Yehya, A., Garcia, R. A., Patel, P., Fudim, M., et al. (2025) · Heart Failure Reviews · doi:10.1007/s10741-025-10512-3
Cardiac conduction system in mammals
Calløe, K., Elbrønd, V. S., Bertelsen, M. F., & Thomsen, M. B. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-24142-0.00007-2
- Authors
- Akar, F. G., Wu, R. C., Deschenes, I., Armoundas, A. A., Piacentino, V., Houser, S. R., & Tomaselli, G. F.
- Affiliations
- Johns Hopkins University (US)
- Temple University (US)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2004-02
- Volume
- 286
- Issue
- 2
- Pages
- H602-H609
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2146487571
- Cited by
- 88
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 8 · 2014: 5 · 2013: 6 · 2012: 4
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- transient outward potassium current, ITO, ventricular myocytes, Kv4.3, Kv1.4, KChIP2, recovery from inactivation, steady-state inactivation, oxidative stress, ventricular repolarization, species differences, post-translational modification
- MeSH terms
- Animals, Anti-Arrhythmia Agents, Coronary Vessels, Dogs, Electrophysiology, Flecainide, Humans, Male, Phenotype, Species Specificity, Potassium Channels, Ventricular Function, Myocytes, Cardiac, In Vitro Techniques
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