Measurement of myofilament calcium in living cardiomyocytes using a targeted genetically encoded indicator

Paul Robinson, Alexander J Sparrow, Connor N Broyles, Kolja Sievert, Yu-Fen Chang, Frances A Brook, Xiaoyu Zhang, Hugh Watkins, Yama A Abassi, Michael A Geeves, Charles Redwood, Matthew J Daniels

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Received: 29th March 18

Visualising when and where calcium appears and disappears in cardiomyocytes is a major goal of cardiovascular research. Surprisingly we find that the chemical dyes widely used for this purpose disrupt cell contractility, due at least in part due to direct inhibition of the acto-myosin ATPase required to generate force. In order to improve calcium detection methods, we have developed a genetically encoded indicator that sits within the myofilament to directly visualisethe changes occurring at the sarcomere. This tool improves on established chemical dyes and untargeted genetically encoded indicators for analysing small molecule modulators of myofilament-based calcium signalling. Importantly this is achieved without any measurable change in contractile function.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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