Gene Structures and Expression Profiles of Three Human KCND (Kv4) Potassium Channels Mediating A-Type Currents ITO and ISA
Abstract
The four known members of the KCND/Kv4 channel family encode voltage-gated potassium channels. Recent studies provide evidence that members of the Kv4 channel family are responsible for native, rapidly inactivating (A-type) currents described in heart (I(TO)) and neurons (I(SA)). In this study, we cloned the human KCND1 cDNA, localized the KCND1 gene to chromosome Xp11.23-p11.3, and determined the genomic structure and tissue-specific expression of the KCND1, KCND2, and KCND3 genes, respectively. The open reading frame of Kv4. 1 is 1941 nucleotides long, predicting a protein of 647 amino acids. The deduced protein sequence of Kv4.1 shows an overall identity of 60% with Kv4.2 and Kv4.3L and corresponds to the common structure of voltage-gated potassium channels. KCND1-specific transcripts were detectable in human brain, heart, liver, kidney, thyroid gland, and pancreas, as revealed by Northern blot and RT-PCR experiments. The comparison of the expression patterns of the known Kv4 family members shows subtype specificity with significant overlaps. The KCND gene structures exhibit an evolutionarily conserved exon pattern with a large first exon containing the intracellular N-terminus and the putative membrane-spanning regions S1 to S5, as well as part of the pore region. The KCND3 gene contains an additional exon of 57 bp, which is not present in the other two KCND genes and gives rise to the C-terminal splice KCND3L variant with an insertion of 19 amino acids.
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Voltage-gated potassium channels regulate dendritic A-type current I (SA) in brain neurons by controlling potassium transport across the excitatory membrane in the brain.
“By controlling potassium transport across the excitatory membrane in the brain, voltage-gated potassium channels regulate dendritic A-type current I (SA) in brain neurons [45].”
Cites
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease
Chirgwin, J. M., Przybyla, A., MacDonald, R. J., & Rutter, W. J. (1979) · Biochemistry · doi:10.1021/bi00591a005 · Cited by 21,725 · see citing works
K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons
Hoffman, D. A., Magee, J. C., Colbert, C. M., & Johnston, D. (1997) · Nature · doi:10.1038/43119 · Cited by 1,392 · see citing works
MiRP1 Forms IKr Potassium Channels with HERG and Is Associated with Cardiac Arrhythmia
Abbott, G. W., Sesti, F., Splawski, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., & Goldstein, S. A. N. (1999) · Cell · doi:10.1016/s0092-8674(00)80728-x · Cited by 1,353 · see citing works
Bailey, A. J., Amaia Hervas, G., Matthews, N., Palferman, S., Wallace, S., Aubin, A., Michelotti, J., Wainhouse, C., Papanikolaou, Κ., Rutter, M. L., et al. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.3.571 · Cited by 537 · 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
Funding for malaria genome sequencing
Hoffman, S., Bancroft, W., Michael, G., James, S., Burroughs, E. C. B., Stephenson, J., & Morgan, M. (1997) · Nature · doi:10.1038/42571 · Cited by 461 · see citing works
Role of the Kv4.3 K+Channel in Ventricular Muscle
Dixon, J. E., Shi, W., Wang, H., McDonald, C., Yu, H., Wymore, R. S., Cohen, I. S., & McKinnon, D. H. (1996) · Circulation Research · doi:10.1161/01.res.79.4.659 · Cited by 433 · see citing works
Alings, M., & Wilde, A. A. M. (1999) · Circulation · doi:10.1161/01.cir.99.5.666 · Cited by 424 · 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
Hoffman, D. A., & Johnston, D. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-10-03521.1998 · Cited by 373 · see citing works
Serôdio, P., & Rudy, B. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.2.1081 · Cited by 343 · see citing works
Crystal structure of the tetramerization domain of the Shaker potassium channel
Kreusch, A., Pfaffinger, P. J., Stevens, C. F., & Choe, S. (1998) · Nature · doi:10.1038/31978 · Cited by 310 · see citing works
Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats.
Dixon, J. E., & McKinnon, D. H. (1994) · Circulation Research · doi:10.1161/01.res.75.2.252 · Cited by 304 · see citing works
Barry, D. M., Xu, H., Schuessler, R. B., & Nerbonne, J. M. (1998) · Circulation Research · doi:10.1161/01.res.83.5.560 · Cited by 291 · see citing works
Maletić‐Savatić, M., Lenn, N., & Trimmer, J. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-05-03840.1995 · Cited by 260 · 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
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
Serôdio, P., de Miera, E. V., & Rudy, B. (1996) · Journal of Neurophysiology · doi:10.1152/jn.1996.75.5.2174 · Cited by 220 · see citing works
Characterization of a mammalian cDNA for an inactivating voltage-sensitive K+ channel
Baldwin, T. J., Tsaur, M.-L., Lopez George, A., Jan, Y. N., & Jan, L. Y. (1991) · Neuron · doi:10.1016/0896-6273(91)90299-f · Cited by 214 · see citing works
Identification of molecular components of A-type channels activating at subthreshold potentials
Serôdio, P., Kentros, C. G., & Rudy, B. (1994) · Journal of Neurophysiology · doi:10.1152/jn.1994.72.4.1516 · Cited by 193 · see citing works
Shen, N. V., & Pfaffinger, P. J. (1995) · Neuron · doi:10.1016/0896-6273(95)90319-4 · Cited by 187 · see citing works
Johns, D. C., Nuss, H. B., & Marbán, E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.50.31598 · Cited by 170 · see citing works
Wickenden, A. (1998) · Cardiovascular Research · doi:10.1016/s0008-6363(97)00256-3 · Cited by 167 · see citing works
Assembly of Voltage-gated Potassium Channels
Xu, J., Yu, W., Jan, Y. N., et al. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.42.24761 · Cited by 166 · see citing works
mShal, a subfamily of A-type K+ channel cloned from mammalian brain.
Pak, M. D., Baker, K. D., Covarrubias, M., Butler, A., Ratcliffe, A., & Salkoff, L. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.10.4386 · Cited by 165 · see citing works
Shal‐type channels contribute to the Ca2+‐independent transient outward K+ current in rat ventricle.
Fiset, C., Clark, R. B., Shimoni, Y., & Giles, W. R. (1997) · The Journal of Physiology · doi:10.1113/jphysiol.1997.sp021998 · Cited by 164 · see citing works
Inactivation Gating of Kv4 Potassium Channels
Jerng, H. H., Shahidullah, M., & Covarrubias, M. (1999) · The Journal of General Physiology · doi:10.1085/jgp.113.5.641 · Cited by 121 · see citing works
Ohya, S., Tanaka, M., Oku, T., et al. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01483-x · Cited by 115 · see citing works
Takimoto, K., Li, D., Hershman, K. M., et al. (1997) · Circulation Research · doi:10.1161/01.res.81.4.533 · Cited by 104 · see citing works
Modulation of Kv4 channels, key components of rat ventricular transient outward K+ current, by PKC
Nakamura, T. Y., Coetzee, W. A., de Miera, E. V., Artman, M., & Rudy, B. (1997) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1997.273.4.h1775 · Cited by 95 · see citing works
Structural determinant for assembly of mammalian K+ channels
Lee, T. E., Philipson, L. H., Kuznetsov, A., & Nelson, D. J. (1994) · Biophysical Journal · doi:10.1016/s0006-3495(94)80840-9 · Cited by 91 · see citing works
Kálmán, K., Nguyen, A., Tseng-Crank, J., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5851 · Cited by 86 · 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
Coexpression of the KCNA3BGene Product with Kv1.5 Leads to a Novel A-type Potassium Channel
Leicher, T., Bähring, R., Isbrandt, D., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.52.35095 · Cited by 78 · see citing works
Self-citationPetersen, K. R., & Nerbonne, J. M. (1999) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240050792 · Cited by 67 · see citing works
Differences in regional distribution of K+ current densities in rat ventricle
Casis, Ó., Iriarte, M. M., Gallego, M., et al. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00287-2 · Cited by 66 · see citing works
Blair, T. A., Roberds, S. L., Tamkun, M. M., et al. (1991) · FEBS Letters · doi:10.1016/0014-5793(91)81420-d · Cited by 66 · see citing works
Zhu, X. R., Wulf, A., Schwarz, M., Isbrandt, D., & Pongs, O. (1999) · PubMed · Cited by 66 · see citing works
Self-citationCloning, expression and CNS distribution of Kv4.3, an A‐type K+ channel α subunit
Tsaur, M.-L., Chou, C.-C., Shih, Y., & Wang, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01388-9 · Cited by 64 · see citing works
Region-specific expression of a K+ channel gene in brain.
Rudy, B., Kentros, C. G., Weiser, M. J., Fruhling, D., Serôdio, P., de Miera, E. V., Ellisman, M. H., Pollock, J. A., & Baker, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.10.4603 · Cited by 61 · see citing works
Cloning and Expression of the Human Kv4.3 Potassium Channel
Dilks, D. D., Ling, H., Cockett, M. I., Sokol, P. T., & Numann, R. E. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.81.4.1974 · Cited by 45 · see citing works
Structure, chromosome localization, and tissue distribution of the mouse twik K+ channel gene
Arrighi, I., Lesage, F., Scimeca, J., et al. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00260-9 · Cited by 40 · see citing works
Genomic Organization of Nematode 4TM K+ Channelsa
WANG, Z., Kunkel, M. T., Wei, A. D., et al. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb11294.x · Cited by 38 · see citing works
Park, J. P., Moeschler, J. B., Hani, V. H., Hawk, A. B., Belloni, D. R., Noll, W. W., & Mohandas, T. K. (1998) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19980630)78:2 · Cited by 18 · see citing works
Molecular mechanisms of arrhythmias.
Janse, M. J., & Wilde, A. A. M. (1998) · PubMed · Cited by 18 · see citing works
Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13.
Albrecht, B. E., Weber, K., & Pongs, O. (1995) · PubMed · Cited by 15 · see citing works
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Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum
Guerrini, R., Conti, V., Mantegazza, M., Balestrini, S., Galanopoulou, A. S., & Benfenati, F. (2023) · Physiological Reviews · doi:10.1152/physrev.00063.2021 · Cited by 196 · see citing works
Modulation of Kv4.2 Channel Expression and Gating by Dipeptidyl Peptidase 10 (DPP10)
Jerng, H. H., Qian, Y., & Pfaffinger, P. J. (2004) · Biophysical Journal · doi:10.1529/biophysj.104.042358 · Cited by 142 · see citing works
Wu, Z., Cai, Z., Shi, H., Huang, X., Cai, M., Yuan, K., Huang, P., Shi, G., Yan, T., & Li, Z. (2022) · Aging · doi:10.18632/aging.204030 · Cited by 37 · see citing works
Schultz, J.-H., Volk, T., Bassalaý, P., Hennings, J. C., Hübner, C. A., & Ehmke, H. (2007) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-006-0203-1 · Cited by 18 · see citing works
- Authors
- Isbrandt, D., Leicher, T., Waldschütz, R., Zhu, X., Luhmann, U., Michel, U., Sauter, K., & Pongs, O.
- Affiliations
- Universität Hamburg (DE)
- University of Göttingen (DE)
- Corresponding author
- Isbrandt, Dirk
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 64
- Issue
- 2
- Pages
- 144-154
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W1969536341
- Cited by
- 86
- References
- 47
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- GRO (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- 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 potassium channels, Kv4.1, Kv4.2, A-type potassium current, Ito current, voltage-gated potassium channels, gene structure, exon structure, tissue-specific gene expression, alternative splicing, cDNA cloning
- MeSH terms
- Chromosome Mapping, Cloning, Molecular, Electric Conductivity, Exons, Humans, Introns, Molecular Sequence Data, RNA, Messenger, Tissue Distribution, Transcription, Genetic, Potassium Channels, Ion Channel Gating, Gene Library, Gene Expression, Polymerase Chain Reaction, Sequence Alignment, Genome, Sequence Homology, Amino Acid, DNA, Complementary, Potassium Channels, Voltage-Gated, Shal Potassium Channels
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