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Novel Perspectives on Cardiac Pacemaker Regulation: Role of the Coupled Function of Sarcolemmal and Intracellular Proteins

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Heart Rate and Rhythm

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.

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Acknowledgments

This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging.

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Authors and Affiliations

  1. NIA Intramural Research Program, Laboratory of Cardiovascular Science, NIH, 5600 Nathan Shock Drive, Baltimore, MA, 21224, USA

    Victor A. Maltsev, Tatiana M. Vinogradova & Edward G. Lakatta

Authors
  1. Victor A. Maltsev
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  2. Tatiana M. Vinogradova
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  3. Edward G. Lakatta
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Corresponding author

Correspondence to Victor A. Maltsev .

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Editors and Affiliations

  1. Life Sciences Academy, Usman Enclave 103, Lucknow, 226024, India

    Onkar N. Tripathi

  2. Medizinische Fakultät, Inst. für Pharmakologie u. Toxikologie, TU Dresden, Fetscherstraße 74, Dresden, 01307, Germany

    Ursula Ravens

  3. Cardiovascular Research &, Training Inst. (CVRTI), University of Utah, South 2000 East 95, Salt Lake City, 84112-5000, Utah, USA

    Michael C. Sanguinetti

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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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