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Annual Review of Physiology

Volume 87, 2025

The Heart Is a Smart Pump: Mechanotransduction Mechanisms of the Frank-Starling Law and the Anrep Effect

  • Ye Chen-Izu1,2,3, Tamas Banyasz1,4, John A. Shaw1,5 and Leighton T. Izu1
  • 1Department of Pharmacology, School of Medicine, University of California, Davis, California, USA; email: [email protected], [email protected] 2Department of Biomedical Engineering, University of California, Davis, California, USA 3Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, California, USA 4Department of Physiology, University of Debrecen, Debrecen, Hungary 5Department of Aerospace Engineering, University of Michigan, Ann Arbor, Michigan, USA
  • Vol. 87:53-77 (Volume publication date February 2025)
  • First published as a Review in Advance on December 03, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

The Frank-Starling law and Anrep effect describe two intrinsic mechanisms that regulate contraction force in the heart. Based on recent advancements and the historical literature, we propose new perspectives and address several critical issues in this review. () The Frank-Starling mechanism and Anrep effect are dynamically linked and act synergistically. () An open question is how cardiomyocytes sense mechanical load and transduce to biochemical signals (called mechano-chemo-transduction or MCT) to regulate contraction in response to load changes. () One research focus is to identify various mechanosensors and decipher their downstream MCT pathways. () Innovative experimental techniques engage different mechanosensors that detect different local strain and stress in the cell architecture. () Closed-loop MCT feedback in the dynamic excitation-Ca2+ signaling-contraction system enables autoregulation of contraction in response to physiological load changes. () However, pathological overload such as volume and pressure overload lead to excessive MCT-Ca2+ gain, cardiac remodeling, and heart diseases.

Keyword(s): autoregulation, Ca2+ signaling, cardiomyocyte, excitation-contraction coupling, heart, mechano-chemo-transduction
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/content/journals/10.1146/annurev-physiol-022724-104846
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The Heart Is a Smart Pump: Mechanotransduction Mechanisms of the Frank-Starling Law and the Anrep Effect
Annual Review of Physiology 87, 53 (2025); https://doi.org/10.1146/annurev-physiol-022724-104846
/content/journals/10.1146/annurev-physiol-022724-104846
/content/journals/10.1146/annurev-physiol-022724-104846
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