Mechano-chemo transduction tunes the heartstrings

In the beating heart, mechanical stretch triggers the production of reactive oxygen or nitrogen species that target Ca(2+)-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 Ca(2+)/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 Ca(2+) 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.