The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Molecular Basis of Transient Outward Potassium Current Downregulation in Human Heart Failure: A Decrease in Kv4.3 mRNA Correlates With a Reduction in Current Density
Open accessAbstract
Background—Despite advances in medical therapy, congestive heart failure remains a major cause of death in the developed world. A disproportionate number of the deaths of patients with heart failure are sudden and presumed to be arrhythmic. Heart failure in humans and in animal models is associated with prolongation of the action potential duration (APD), the result of downregulation of K+currents—prominently, the Ca 2+-independent transient outward current (Ito). The mechanism for the reduction of Ito in heart failure is unknown. The K+channel α-subunit Kv4.3, a homolog of the Drosophila Shal family, is most likely to encode all or part of the native cardiac Ito in humans. Methods and Results—We used ribonuclease protection assays and whole-cell electrophysiological recording to study changes in the level of Kv4.3 mRNA and Ito in human tissues and isolated ventricular myocytes, respectively. We found that the level of Kv4.3 mRNA decreased by 30% in failing hearts compared with nonfailing controls. Furthermore, this reduction correlated with the reduction in peak Ito density measured in ventricular myocytes isolated from adjacent regions of the heart. There was no significant change in the steady-state level of any other mRNA studied (HERG, Kv1.4, Kir2.1, Kvβ1.3, and the α1C subunit of the Ca 2+channel). mRNAs encoding Kv1.2, Kv1.5, and Kv2.1 were found in low abundance in human ventricle. Conclusions—These data provide further support for the hypothesis that Kv4.3 encodes all or part of the native cardiac Ito in humans and that part of the downregulation of this current in heart failure may be transcriptionally regulated.
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Metadata
- Authors
- Kääb, S., Dixon, J., Duc, J., Ashen, D., Näbauer, M., Beuckelmann, D. J., Steinbeck, G., McKinnon, D., & Tomaselli, G. F.
- Venue
- Circulation
- Published
- 1998-10-06
- Volume
- 98
- Issue
- 14
- Pages
- 1383-1393
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2107351696
- Cited by
- 401
- References
- 43
- FWCI
- 13.85
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Molecular Basis of Transient Outward Potassium Current Downregulation in Human Heart Failure: A Decrease in Kv4.3 mRNA Correlates With a Reduction in Current Density. https://app.cochat.ai/papers/10.1161/01.cir.98.14.1383
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- Kääb, S., Dixon, J., Duc, J., Ashen, D., Näbauer, M., Beuckelmann, D. J., Steinbeck, G., McKinnon, D., & Tomaselli, G. F. (1998). Molecular Basis of Transient Outward Potassium Current Downregulation in Human Heart Failure: A Decrease in Kv4.3 mRNA Correlates With a Reduction in Current Density. Circulation. https://doi.org/10.1161/01.cir.98.14.1383
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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