Abstract
The pacemaker cells of the heart initiate the heartbeat, sustain the circulation, and dictate the rate and rhythm of cardiac contraction1. Circulatory collapse ensues when these specialized cells are damaged by disease, a situation that currently necessitates the implantation of an electronic pacemaker2. Here we report the use of viral gene transfer to convert quiescent heart-muscle cells into pacemaker cells, and the successful generation of spontaneous, rhythmic electrical activity in the ventricle in vivo. Our results indicate that genetically engineered pacemakers could be developed as a possible alternative to implantable electronic devices.
Similar content being viewed by others
References
Brooks, C. M. & Lu, H.-H The Sinoatrial Pacemaker of the Heart (Thomas, Springfield, Illinois, 1972).
Kusumoto, F. M. & Goldschlager, N. N. Engl. J. Med. 334, 89–97 (1996).
Wobus, A. M., Rohwedel, J., Maltsev, V. & Hescheler, J. Ann. NY Acad. Sci. 752, 460–469 (1995).
Kubo, Y., Baldwin, T. J., Jan, Y. N. & Jan, L. Y. Nature 362, 127–333 (1993).
Herskowitz, I. Nature 329, 219–222 (1987).
Slesinger, P. A. et al. Neuron 16, 321–331 (1996).
Irisawa, H., Brown, H. F. & Giles, W. Physiol. Rev. 73, 197–227 (1993).
Santoro, B. & Tibbs, G. R. Ann. NY Acad. Sci. 868, 741–764 (1999).
Imoto, Y., Ehara, T. & Matsuura, H. Am. J. Physiol. 252, 325–333 (1987).
Hirano, Y. & Hiraoka, M. J. Physiol. (Lond.) 395, 455–472 (1988).
Rodriguez-Contreras, A., Nonner, W. & Yamoah, E. N. J. Physiol. (Lond.) 538, 729–745 (2002).
Campbell, D. L., Giles, W. R. & Shibata, E. F. J. Physiol. (Lond.) 403, 239–266 (1988).
Brown, H. F., Kimura, J., Noble, D., Noble, S. J. & Taupignon, A. Proc. R. Soc. Lond. B 222, 329–347 (1984).
Author information
Authors and Affiliations
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Miake, J., Marbán, E. & Nuss, H. Biological pacemaker created by gene transfer. Nature 419, 132–133 (2002). https://doi.org/10.1038/419132b
Issue Date:
DOI: https://doi.org/10.1038/419132b
- Springer Nature Limited
This article is cited by
-
Harnessing cell reprogramming for cardiac biological pacing
Journal of Biomedical Science (2023)
-
Analysis of Circulating Waves in Tissue Rings derived from Human Induced Pluripotent Stem Cells
Scientific Reports (2020)
-
A study of the outward background current conductance gK1, the pacemaker current conductance gf, and the gap junction conductance gj as determinants of biological pacing in single cells and in a two-cell syncytium using the dynamic clamp
Pflügers Archiv - European Journal of Physiology (2020)
-
Ionic and cellular mechanisms underlying TBX5/PITX2 insufficiency-induced atrial fibrillation: Insights from mathematical models of human atrial cells
Scientific Reports (2018)
-
Next-generation pacemakers: from small devices to biological pacemakers
Nature Reviews Cardiology (2018)