Mechano-Chemo Transduction Tunes the Heartstrings

Sci. Signal., 18 March 2014
Vol. 7, Issue 317, p. pe7
DOI: 10.1126/scisignal.2005214

Mechano-Chemo Transduction Tunes the Heartstrings

  1. Benjamin L. Prosser1,* and
  2. Christopher W. Ward2,3,*
  1. 1Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  2. 2Department of Organizational Systems and Adult Health, University of Maryland School of Nursing, Baltimore, MD 21201, USA.
  3. 3Center for Biomedical Engineering and Technology (BioMET), University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  1. *Corresponding author. E-mail: ward{at}son.umaryland.edu (C.W.W.); bpros{at}mail.med.upenn.edu (B.L.P.)

Abstract

In the beating heart, mechanical stretch triggers the production of reactive oxygen or nitrogen species that target Ca2+-signaling proteins. Termed mechano-chemo transduction, this pathway “tunes” the calcium release machinery in the healthy heart; when dysregulated, it contributes to disease. In this issue of Science Signaling, Jian et al. used a “cell-in-gel” method to show that contractions in healthy heart cells elicit a steep, viscosity-dependent increase in mechano-chemo transduction in which nitric oxide synthase (NOS), NADPH oxidase 2 (Nox2), and Ca2+/calmodulin-dependent kinase II (CaMKII) contribute. These authors provide evidence for a role of neuronal NOS (nNOS) over endothelial NOS; they supported their findings with super-resolution microscopy, which localized nNOS nearest to the Ca2+ release sites. In a disease model, signaling through nNOS and CaMKII rather than through Nox2 was enhanced, supporting the independent mechano-activation of these enzymes. The coupling of these quantitative approaches will provide a new understanding of mechano-chemo transduction.

Citation:

B. L. Prosser and C. W. Ward, Mechano-Chemo Transduction Tunes the Heartstrings. Sci. Signal. 7, pe7 (2014).

Mechanotransduction in Cardiac Hypertrophy and Failure
R. C. Lyon, F. Zanella, J. H. Omens, and F. Sheikh
Circ. Res. 116, 1462-1476 (10 April 2015)

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