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Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel.
Open accessAbstract
The principal voltage-sensitive sodium channel from human heart has been cloned, sequenced, and functionally expressed. The cDNA, designated hH1, encodes a 2016-amino acid protein that is homologous to other members of the sodium channel multigene family and bears greater than 90% identity to the tetrodotoxin-insensitive sodium channel characteristic of rat heart and of immature and denervated rat skeletal muscle. Northern blot analysis demonstrates an approximately 9.0-kilobase transcript expressed in human atrial and ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. When expressed in Xenopus oocytes, hH1 exhibits rapid activation and inactivation kinetics similar to native cardiac sodium channels. The single channel conductance of hH1 to sodium ions is about twice that of the homologous rat channel and hH1 is more resistant to block by tetrodotoxin (IC50 = 5.7 microM). hH1 is also resistant to mu-conotoxin but sensitive to block by therapeutic concentrations of lidocaine in a use-dependent manner.
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Citations
Cited by
Resurgence of sodium channel research
Goldin, A. L. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.871 · Cited by 688
Nabel, E. G. (2003) · New England Journal of Medicine · doi:10.1056/nejmra035098 · Cited by 431
Papadatos, G. A., Wallerstein, P. M. R., Head, C. E. G., Ratcliff, R., Brady, P. A., Benndorf, K., Saumarez, R. C., Trezise, A. E. O., Huang, C. L.-H., Vandenberg, J. I., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082121299 · Cited by 386
Inherited disorders of voltage-gated sodium channels
George, A. L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25505 · Cited by 365
Self-citationMultiple Mechanisms of Na + Channel– Linked Long-QT Syndrome
Dumaine, R., Wang, Q., Keating, M. T., Hartmann, H. A., Schwartz, P. J., Brown, A. M., & Kirsch, G. E. (1996) · Circulation Research · doi:10.1161/01.res.78.5.916 · Cited by 344
Metadata
- Authors
- Gellens, M. E., George, A. L., Chen, L. Q., Chahine, M., Horn, R., Barchi, R. L., & Kallen, R. G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1992-01-15
- Volume
- 89
- Issue
- 2
- Pages
- 554-558
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2027085605
- Cited by
- 628
- References
- 0
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- green
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- Gellens, M. E., George, A. L., Chen, L. Q., Chahine, M., Horn, R., Barchi, R. L., & Kallen, R. G. (1992). Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.89.2.554
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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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