The Emergence of a General Theory of the Initiation and Strength of the Heartbeat
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- Maltsev Victor A.
- Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging Intramural Research Program, National Institutes of Health, USA
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- Vinogradova Tatiana M.
- Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging Intramural Research Program, National Institutes of Health, USA
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- Lakatta Edward G.
- Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging Intramural Research Program, National Institutes of Health, USA
Bibliographic Information
- Other Title
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- Emergence of a General Theory of the Initiation and Strength of the Heartbeat
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Abstract
Sarcoplasmic reticulum (SR) Ca2+ cycling, that is, the Ca2+ clock, entrained by externally delivered action potentials has been a major focus in ventricular myocyte research for the past 5 decades. In contrast, the focus of pacemaker cell research has largely been limited to membrane-delimited pacemaker mechanisms (membrane clock) driven by ion channels, as the immediate cause for excitation. Recent robust experimental evidence, based on confocal cell imaging, and supported by numerical modeling suggests a novel concept: the normal rhythmic heart beat is governed by the tight integration of both intracellular Ca2+ and membrane clocks. In pacemaker cells the intracellular Ca2+ clock is manifested by spontaneous, rhythmic submembrane local Ca2+ releases from SR, which are tightly controlled by a high degree of basal and reserve PKA-dependent protein phosphorylation. The Ca2+ releases rhythmically activate Na+/Ca2+ exchange inward currents that ignite action potentials, whose shape and ion fluxes are tuned by the membrane clock which, in turn, sustains operation of the intracellular Ca2+ clock. The idea that spontaneous SR Ca2+ releases initiate and regulate normal automaticity provides the key that reunites pacemaker and ventricular cell research, thus evolving a general theory of the initiation and strength of the heartbeat.<br>
Journal
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 100 (5), 338-369, 2006
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390001205177111168
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- NII Article ID
- 10018238109
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- NII Book ID
- AA11806667
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- COI
- 1:STN:280:DC%2BD28zot1amtA%3D%3D
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- ISSN
- 13478648
- 13478613
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- NDL BIB ID
- 7963150
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- PubMed
- 16799255
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed