Emergence of mechano-sensitive contraction autoregulation in cardiomyocytes

Leighton Izu, Rafael Shimkunas, Zhong Jian, Bence Hegyi, Mohammad Kazemi-Lari, Anthony Baker, John Shaw, Tamas Banyasz, Ye Chen-Izu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The heart has two intrinsic mechanisms to enhance contractile strength that compensate for increased mechanical load to help maintain cardiac output. When vascular resistance increases the ventricular chamber initially expands causing an immediate length-dependent increase of contraction force via the Frank-Starling mechanism. Additionally, the stress-dependent Anrep effect slowly increases contraction force that results in the recovery of the chamber volume towards its initial state. The Anrep effect poses a paradox: how can the cardiomyocyte maintain higher contractility even after the cell length has recovered its initial length? Here we propose a surface mechanosensor model that enables the cardiomyocyte to sense different mechanical stresses at the same mechanical strain. The cell-surface mechanosensor is coupled to a mechano-chemo-transduction feedback mechanism involving three elements: surface mechanosensor strain, intracellular Ca2+ transient, and cell strain. We show that in this simple yet general system, contractility autoregulation naturally emerges, enabling the cardiomyocyte to maintain contraction amplitude despite changes in a range of afterloads. These nontrivial model predictions have been experimentally confirmed. Hence, this model provides a new conceptual framework for understanding the contractility autoregulation in cardiomyocytes, which contributes to the heart’s intrinsic adaptivity to mechanical load changes in health and diseases.

Original languageEnglish (US)
Article number503
JournalLife
Volume11
Issue number6
DOIs
StatePublished - 2021

Keywords

  • Anrep effect
  • Autoregulation
  • Cardiomyocyte
  • Contractility
  • Mathematical analysis
  • Mathematical model
  • Mechano-chemo-transduction

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Space and Planetary Science
  • Palaeontology

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