Abstract
The pacemaker cells of the heart initiate the heartbeat, sustain the circulation, and dictate the rate and rhythm of cardiac contraction. Circulatory collapse ensues when these specialized cells are damaged by disease, a situation that currently necessitates the implantation of an electronic pacemaker. 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.
MeSH terms
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Action Potentials
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Adenoviridae / genetics
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Amino Acid Substitution / genetics
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Animals
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Calcium Channels, L-Type / metabolism
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Electric Conductivity
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Electrocardiography
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Genes, Dominant / genetics
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Genetic Therapy / methods*
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Genetic Vectors / genetics
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Guinea Pigs
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Heart Diseases / genetics*
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Heart Diseases / therapy*
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Heart Ventricles / cytology
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Heart Ventricles / physiopathology
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Myocardium / metabolism
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Potassium / metabolism
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Potassium Channels, Inwardly Rectifying / genetics*
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Potassium Channels, Inwardly Rectifying / metabolism*
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Transduction, Genetic
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Transgenes / genetics*
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Ventricular Function*
Substances
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Calcium Channels, L-Type
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Potassium Channels, Inwardly Rectifying
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Potassium