| First Author | Abraham DM | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 11 | Pages | 4843-4855 |
| PubMed ID | 30153110 | Mgi Jnum | J:292023 |
| Mgi Id | MGI:6276438 | Doi | 10.1172/JCI95945 |
| Citation | Abraham DM, et al. (2018) The two-pore domain potassium channel TREK-1 mediates cardiac fibrosis and diastolic dysfunction. J Clin Invest 128(11):4843-4855 |
| abstractText | Cardiac two-pore domain potassium channels (K2P) exist in organisms from Drosophila to humans; however, their role in cardiac function is not known. We identified a K2P gene, CG8713 (sandman), in a Drosophila genetic screen and show that sandman is critical to cardiac function. Mice lacking an ortholog of sandman, TWIK-related potassium channel (TREK-1, also known Kcnk2), exhibit exaggerated pressure overload-induced concentric hypertrophy and alterations in fetal gene expression, yet retain preserved systolic and diastolic cardiac function. While cardiomyocyte-specific deletion of TREK-1 in response to in vivo pressure overload resulted in cardiac dysfunction, TREK-1 deletion in fibroblasts prevented deterioration in cardiac function. The absence of pressure overload-induced dysfunction in TREK-1-KO mice was associated with diminished cardiac fibrosis and reduced activation of JNK in cardiomyocytes and fibroblasts. These findings indicate a central role for cardiac fibroblast TREK-1 in the pathogenesis of pressure overload-induced cardiac dysfunction and serve as a conceptual basis for its inhibition as a potential therapy. |
