| First Author | Eden M | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11317 | PubMed ID | 27122098 |
| Mgi Jnum | J:306481 | Mgi Id | MGI:6711122 |
| Doi | 10.1315/11317 | Citation | Eden M, et al. (2016) Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression. Nat Commun 7:11317 |
| abstractText | Calcium signalling plays a critical role in the pathogenesis of heart failure. Here we describe a cardiac protein named Myoscape/FAM40B/STRIP2, which directly interacts with the L-type calcium channel. Knockdown of Myoscape in cardiomyocytes decreases calcium transients associated with smaller Ca(2+) amplitudes and a lower diastolic Ca(2+) content. Likewise, L-type calcium channel currents are significantly diminished on Myoscape ablation, and downregulation of Myoscape significantly reduces contractility of cardiomyocytes. Conversely, overexpression of Myoscape increases global Ca(2+) transients and enhances L-type Ca(2+) channel currents, and is sufficient to restore decreased currents in failing cardiomyocytes. In vivo, both Myoscape-depleted morphant zebrafish and Myoscape knockout (KO) mice display impairment of cardiac function progressing to advanced heart failure. Mechanistically, Myoscape-deficient mice show reduced L-type Ca(2+)currents, cell capacity and calcium current densities as a result of diminished LTCC surface expression. Finally, Myoscape expression is reduced in hearts from patients suffering of terminal heart failure, implying a role in human disease. |
