The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Engineered calmodulins reveal the unexpected eminence of Ca 2+ channel inactivation in controlling heart excitation
Open accessAbstract
Engineered calmodulins (CaMs), rendered Ca 2+ -insensitive by mutations, function as dominant negatives in heterologous systems, and have revealed mechanisms of ion channel modulation by Ca 2+ /CaM. The use of these CaMs in native mammalian cells now emerges as a strategy to unmask the biology of such Ca 2+ feedback. Here, we developed recombinant adenoviruses bearing engineered CaMs to facilitate their expression in adult heart cells, where Ca 2+ regulation may be essential for moment-to-moment control of the heartbeat. Engineered CaMs not only eliminated the Ca 2+ -dependent inactivation of native calcium channels, but exposed an unexpectedly large impact of removing such feedback: the unprecedented (4- to 5-fold) prolongation of action potentials. This striking result recasts the basic paradigm for action-potential control and illustrates the promise of virally delivered engineered CaM to investigate the biology of numerous other CaM-signaling pathways.
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Marbán, E. (2002) · Nature · doi:10.1038/415213a · Cited by 328
Cited by
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Zhang, R., Khoo, M. S. C., Wu, Y., Yang, Y., Grueter, C. E., Ni, G., Price, E. E., Thiel, W., Guatimosim, S., Song, L.-S., et al. (2005) · Nature Medicine · doi:10.1038/nm1215 · Cited by 579
Unified Mechanisms of Ca2+ Regulation across the Ca2+ Channel Family
Liang, H., DeMaria, C. D., Erickson, M. G., Mori, M. X., Alseikhan, B. A., & Yue, D. T. (2003) · Neuron · doi:10.1016/s0896-6273(03)00560-9 · Cited by 305
Self-citationA modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels
Dick, I. E., Tadross, M. R., Liang, H., Tay, L. H., Yang, W., & Yue, D. T. (2008) · Nature · doi:10.1038/nature06529 · Cited by 254
Self-citationCa2+-dependent modulation of voltage-gated Ca2+ channels
Christel, C., & Lee, A. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.12.012 · Cited by 112
Yarotskyy, V., Gao, G., Peterson, B. Z., & Elmslie, K. S. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2008.161737 · Cited by 76
Metadata
- Authors
- Alseikhan, B. A., DeMaria, C. D., Colecraft, H. M., & Yue, D. T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-12-16
- Volume
- 99
- Issue
- 26
- Pages
- 17185-17190
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2001594716
- Cited by
- 186
- References
- 1
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Engineered calmodulins reveal the unexpected eminence of Ca 2+ channel inactivation in controlling heart excitation. https://app.cochat.ai/papers/10.1073/pnas.262372999
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- Alseikhan, B. A., DeMaria, C. D., Colecraft, H. M., & Yue, D. T. (2002). Engineered calmodulins reveal the unexpected eminence of Ca 2+ channel inactivation in controlling heart excitation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.262372999
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