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  • Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response.

Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response.

Nature communications (2016-10-27)
Jenna Scotcher, Oleksandra Prysyazhna, Andrii Boguslavskyi, Kornel Kistamas, Natasha Hadgraft, Eva D Martin, Jenny Worthington, Olena Rudyk, Pedro Rodriguez Cutillas, Friederike Cuello, Michael J Shattock, Michael S Marber, Maria R Conte, Adam Greenstein, David J Greensmith, Luigi Venetucci, John F Timms, Philip Eaton
摘要

The Frank-Starling mechanism allows the amount of blood entering the heart from the veins to be precisely matched with the amount pumped out to the arterial circulation. As the heart fills with blood during diastole, the myocardium is stretched and oxidants are produced. Here we show that protein kinase G Iα (PKGIα) is oxidant-activated during stretch and this form of the kinase selectively phosphorylates cardiac phospholamban Ser16-a site important for diastolic relaxation. We find that hearts of Cys42Ser PKGIα knock-in (KI) mice, which are resistant to PKGIα oxidation, have diastolic dysfunction and a diminished ability to couple ventricular filling with cardiac output on a beat-to-beat basis. Intracellular calcium dynamics of ventricular myocytes isolated from KI hearts are altered in a manner consistent with impaired relaxation and contractile function. We conclude that oxidation of PKGIα during myocardial stretch is crucial for diastolic relaxation and fine-tunes the Frank-Starling response.

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Anti-Myosin Antibody, slow muscle, clone NOQ7.5.4D, clone NOQ7.5.4D, Chemicon®, from mouse
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