PerspectiveCell Biology

Mechano-Chemo Transduction Tunes the Heartstrings

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

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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.

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