| First Author | Scotcher J | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13187 | PubMed ID | 27782102 |
| Mgi Jnum | J:242643 | Mgi Id | MGI:5905939 |
| Doi | 10.1038/ncomms13187 | Citation | Scotcher J, et al. (2016) Disulfide-activated protein kinase G Ialpha regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response. Nat Commun 7:13187 |
| abstractText | 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 Ialpha (PKGIalpha) 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 PKGIalpha knock-in (KI) mice, which are resistant to PKGIalpha 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 PKGIalpha during myocardial stretch is crucial for diastolic relaxation and fine-tunes the Frank-Starling response. |
