Molecular and functional characterization of Kv4.2 and KChIP2 expressed in the porcine left ventricle
Abstract
Recent studies showed that the Ca(2+)-independent transient outward current (I (to)) is very small or even not detectable in the porcine left ventricle. We investigated whether an altered molecular expression or function of voltage-dependent potassium channels belonging to the Kv4 sub-family and their ancillary Ca(2+)-binding beta sub-unit KChIP2, which contribute to the major fraction of I (to )in other species, may underlie this lack of a significant I (to) in the porcine left ventricle. RT-PCR analysis with degenerate primers showed that both Kv4 mRNA and KChIP2 mRNA are expressed in porcine left ventricular tissue and in isolated ventricular myocytes. PCR cloning and sequence analysis predicted proteins with >98% identity to rat and human Kv4.2 and >99% identity to rat and human KChIP2. Heterologous expression of porcine Kv4.2 in Xenopus laevis oocytes gave rise to currents with characteristic properties of rat and human Kv4.2, and co-expression with its KChIP2 sub-unit increased current density (tenfold), slowed inactivation (twofold) and accelerated recovery from inactivation (tenfold). Kv4.2 immunohistochemistry in porcine left ventricular tissue revealed a predominant membrane-bound signal. Relative quantification of gene expression indicated that Kv4.2 and KChIP2 mRNA and protein are expressed at comparable ratios in porcine and rat left ventricular tissues, which displays a large I (to). Collectively, these data demonstrate that the lack of a significant I (to) in the porcine left ventricle does not result from dysfunctional or insufficiently expressed Kv4.2 and KChIP2 sub-units.
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Other differences between swine and human include small or lack of transient outward current (Ito) in swine and purkinje fiber distribution.
“Other differences include small or lack of transient outward current (Ito) in swine (Lacroix, et al., 2002; G. R. Li, et al., 2003; Schultz, et al., 2007) and purkinje fiber distribution (Hamlin, 2007).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Schultz, et al., 2007
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
Hamill, O. P., Marty, A., Neher, E., Sakmann, B., & Sigworth, F. J. (1981) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00656997 · Cited by 18,436 · see citing works
Down-Regulation of Na+/K+ATPase Activity by Human Parvovirus B19 Capsid Protein VP1
Almilaji, A., Szteyn, K., Fein, E., Pakladok, T., Muñoz, C., Elvira, B., Towhid, S. T., Alesutan, I., Shumilina, E. V., Bock, C. –., et al. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350083 · Cited by 8,675 · see citing works
Regulation of the Voltage Gated K+ Channel Kv1.3 by Recombinant Human Klotho Protein
Almilaji, A., Honisch, S., Liu, G., Elvira, B., Ajay, S. S., Hosseinzadeh, Z., Ahmed, M., Muñoz, C., Sopjani, M., & Lang, F. (2014) · Kidney & Blood Pressure Research · doi:10.1159/000368472 · Cited by 5,592 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · 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
Subcellular segregation of two A-type K+ channel proteins in rat central neurons
Sheng, M., Tsaur, M.-L., Jan, Y. N., & Jan, L. Y. (1992) · Neuron · doi:10.1016/0896-6273(92)90166-b · Cited by 469 · see citing works
Liu, D. W., Gintant, G. A., & Antzelevitch, C. (1993) · Circulation Research · doi:10.1161/01.res.72.3.671 · Cited by 462 · see citing works
Näbauer, M., Beuckelmann, D. J., Überfuhr, P., & Steinbeck, G. (1996) · Circulation · doi:10.1161/01.cir.93.1.168 · Cited by 459 · see citing works
Transient 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
Schram, G., Pourrier, M., Melnyk, P. M., & Nattel, S. (2002) · Circulation Research · doi:10.1161/01.res.0000018627.89528.6f · Cited by 427 · see citing works
Structure and Function of Kv4-Family Transient Potassium Channels
Birnbaum, S. G., Varga, A. W., Yuan, L., Anderson, A. E., Sweatt, J. D., & Schrader, L. A. (2004) · Physiological Reviews · doi:10.1152/physrev.00039.2003 · Cited by 369 · see citing works
Transient outward current in human ventricular myocytes of subepicardial and subendocardial origin.
Wettwer, E., Amos, G. J., Posival, H., & Ravens, U. (1994) · Circulation Research · doi:10.1161/01.res.75.3.473 · Cited by 365 · see citing works
Four Kinetically Distinct Depolarization-activated K+ Currents in Adult Mouse Ventricular Myocytes
Xu, H., Guo, W., & Nerbonne, J. M. (1999) · The Journal of General Physiology · doi:10.1085/jgp.113.5.661 · Cited by 313 · see citing works
Apkon, M., & Nerbonne, J. M. (1991) · The Journal of General Physiology · doi:10.1085/jgp.97.5.973 · Cited by 295 · see citing works
Rosati, 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
Differential Expression of Voltage-Gated K + Channel Subunits in Adult Rat Heart
Barry, D. M., Trimmer, J. S., Merlie, J. P., & Nerbonne, J. M. (1995) · Circulation Research · doi:10.1161/01.res.77.2.361 · Cited by 255 · see citing works
Shibata, R., Misonou, H., Campomanes, C. R., Anderson, A. E., Schrader, L. A., Doliveira, L. C., Carroll, K. I., Sweatt, J. D., Rhodes, K. J., & Trimmer, J. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306142200 · Cited by 253 · see citing works
Roberds, S. L., & Tamkun, M. M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.5.1798 · Cited by 248 · see citing works
Heterogeneity of action potential waveforms and potassium currents in rat ventricle
Clark, R. B., Bouchard, R. A., Salinas-Stefanon, E. M., Sánchez‐Chapula, J. A., & Giles, W. R. (1993) · Cardiovascular Research · doi:10.1093/cvr/27.10.1795 · Cited by 228 · see citing works
Genetic Manipulation of Cardiac K + Channel Function in Mice
Nerbonne, J. M., Nichols, C. G., Schwarz, T. L., & Escande, D. (2001) · Circulation Research · doi:10.1161/hh2301.100349 · Cited by 227 · 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
Bähring, R., Dannenberg, J., Peters, H. C., Leicher, T., Pongs, O., & Isbrandt, D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101320200 · Cited by 204 · see citing works
Transient outward current in human and rat ventricular myocytes
Wettwer, E., Amos, G. J., Gath, J., Zerkowski, H. R., Reidemeister, J., & Ravens, U. (1993) · Cardiovascular Research · doi:10.1093/cvr/27.9.1662 · Cited by 131 · see citing works
Rosati, B., Grau, F. R., Rodriguez, S., Li, H., Nerbonne, J. M., & McKinnon, D. H. (2003) · The Journal of Physiology · doi:10.1111/j..2003.t01-1-00815.x · Cited by 103 · see citing works
Isbrandt, D., Leicher, T., Waldschütz, R., Zhu, X., Luhmann, U., Michel, U., Sauter, K., & Pongs, O. (2000) · Genomics · doi:10.1006/geno.2000.6117 · Cited by 86 · see citing works
Volk, T., Nguyen, T. H., Schultz, J., & Ehmke, H. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.0841n.x · Cited by 85 · see citing works
Self-citationMukherjee, R. D., Hewett, K. W., Walker, J. D., Basler, C. G., & Spinale, F. G. (1998) · Cardiovascular Research · doi:10.1016/s0008-6363(97)00128-4 · Cited by 84 · see citing works
Rosati, B., Grau, F. R., Rodriguez, S., et al. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.033704 · Cited by 82 · see citing works
Modulation of electrical heterogeneity by compensated hypertrophy in rat left ventricle
Gomez, A. M., Bénitah, J., Henzel, D., Vinet, A., Lorente, P., & Delgado, C. (1997) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1997.272.3.h1078 · Cited by 78 · 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
Li, G., Du, X., Siow, Y. L., O, K., Tse, H.-F., & LAU, C. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00859-3 · Cited by 75 · see citing works
Matsuda, H. (1986) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00657502 · Cited by 73 · see citing works
Heterogeneous expression of KChIP2 isoforms in the ferret heart
Patel, S. P., Campbell, D. L., Morales, M. J., & Strauss, H. C. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2001.015156 · Cited by 69 · see citing works
Martínez‐Rubio, A., Schwammenthal, Y., Schwammenthal, E., Block, M. S., Reinhardt, L., Garcı́a-Alberola, A., Sierra, G., Shenasa, M., Haverkamp, W., Scheld, H. H., et al. (1997) · Circulation · doi:10.1161/01.cir.96.2.500 · Cited by 57 · see citing works
Masking of A-type K+ channel in guinea pig cardiac cells by extracellular Ca2+
Inoue, M., & Imanaga, I. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.264.6.c1434 · Cited by 45 · see citing works
Bailly, P., Bénitah, J., Mouchonière, M., Vassort, G., & Lorente, P. (1997) · Circulation · doi:10.1161/01.cir.96.4.1266 · Cited by 43 · see citing works
Calcium Channel Types in Cardiac Myocytes
Hess, P. E., Lansman, J. B., Nilius, B., & Tsien, R. W. (1986) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-198600089-00002 · Cited by 37 · see citing works
Lacroix, D. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00236-5 · Cited by 37 · see citing works
Schultz, J., Volk, T., & Ehmke, H. (2001) · Circulation Research · doi:10.1161/01.res.88.5.483 · Cited by 29 · see citing works
Self-citationCalcium Channel Types in Cardiac Myocytes
Hess, P. E., Lansman, J. B., Nilius, B., et al. (1986) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-198611001-00002 · Cited by 27 · see citing works
Mačianskienė, R., Moccia, F. D., Sipido, K. R., Flameng, W. J., & Mubagwa, K. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00952.2001 · Cited by 24 · see citing works
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- Authors
- Schultz, J.-H., Volk, T., Bassalaý, P., Hennings, J. C., Hübner, C. A., & Ehmke, H.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Corresponding author
- Ehmke, Heimo
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2007-01-23
- Volume
- 454
- Issue
- 2
- Pages
- 195-207
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- OpenAlex
- W2093313615
- Cited by
- 18
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2017: 3 · 2016: 2 · 2015: 1 · 2013: 1
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pflügers Archiv - European Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- Kv4.2, KChIP2, transient outward current, voltage-gated potassium channels, ventricular myocytes, channel inactivation kinetics, recovery from inactivation, gene expression, Xenopus oocyte expression, immunohistochemistry
- MeSH terms
- Amino Acid Sequence, Animals, Barium, Cadmium, Calcium, Cloning, Molecular, Electric Stimulation, Electrophysiology, Female, Heart, Male, Membrane Potentials, Molecular Sequence Data, Oocytes, Xenopus laevis, 4-Aminopyridine, Gene Expression, Ventricular Function, Rats, Sprague-Dawley, Sequence Homology, Amino Acid, Myocytes, Cardiac, Sus scrofa, Rats, Kv Channel-Interacting Proteins, Shal Potassium Channels
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