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

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. (a) The Frank-Starling mechanism and Anrep effect are dynamically linked and act synergistically. (b) 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. (c) One research focus is to identify various mechanosensors and decipher their downstream MCT pathways. (d) Innovative experimental techniques engage different mechanosensors that detect different local strain and stress in the cell architecture. (e) Closed-loop MCT feedback in the dynamic excitation-Ca2+ signaling-contraction system enables autoregulation of contraction in response to physiological load changes. ( f ) However, pathological overload such as volume and pressure overload lead to excessive MCT-Ca2+ gain, cardiac remodeling, and heart diseases.