Abstract
Recent experimental and theoretical studies demonstrate that the sinoatrial node cells (SANCs), the primary pacemaker cells of heart, operate as a complex system of functionally coupled sarcolemmal and intracellular proteins. The proteins of this system dynamically (beat-to-beat) interact throughout the entire pacemaker cycle via membrane voltage and local subsarcolemmal Ca2+ changes. Furthermore, functions of the sarcolemmal (SL) electrogenic proteins and sarcoplasmic reticulum (SR) Ca2+ cycling proteins are coupled and regulated enzymatically via Ca2+-, PKA-, and CaMKII-dependent protein phosphorylation. The system is not only robust (i.e., fail-safe within wide parameter range), but simultaneously flexible, because the autonomic neural modulation of the beating rate, via G protein-coupled receptor (GPCR) signaling, acts upon the very same regulatory factors (i.e., the coupling factors, Ca2+, PKA, and CaMKII) that ensure and regulate robust system function in the basal state. This chapter summarizes the experimental and theoretical evidences for this novel pacemaker concept.
Keywords
- Sarcoplasmic Reticulum
- Pacemaker Cell
- Beating Rate
- Diastolic Depolarization
- Sarcoplasmic Reticulum Function
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging.
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Maltsev, V.A., Vinogradova, T.M., Lakatta, E.G. (2011). Novel Perspectives on Cardiac Pacemaker Regulation: Role of the Coupled Function of Sarcolemmal and Intracellular Proteins. In: Tripathi, O., Ravens, U., Sanguinetti, M. (eds) Heart Rate and Rhythm. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17575-6_4
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