| First Author | Li Z | Year | 2017 |
| Journal | Eur J Pharmacol | Volume | 807 |
| Pages | 117-126 | PubMed ID | 28428008 |
| Mgi Jnum | J:253421 | Mgi Id | MGI:6109903 |
| Doi | 10.1016/j.ejphar.2017.04.020 | Citation | Li Z, et al. (2017) Force development and intracellular Ca(2+) in intact cardiac muscles from gravin mutant mice. Eur J Pharmacol 807:117-126 |
| abstractText | Gravin (AKAP12) is an A-kinase-anchoring-protein that scaffolds protein kinase A (PKA), beta2-adrenergic receptor (beta2-AR), protein phosphatase 2B and protein kinase C. Gravin facilitates beta2-AR-dependent signal transduction through PKA to modulate cardiac excitation-contraction coupling and its removal positively affects cardiac contraction. Trabeculae from the right ventricles of gravin mutant (gravin-t/t) mice were employed for force determination. Simultaneously, corresponding intracellular Ca(2+) transient ([Ca(2+)]i) were measured. Twitch force (Tf)-interval relationship, [Ca(2+)]i-interval relationship, and the rate of decay of post-extrasysolic potentiation (Rf) were also obtained. Western blot analysis were performed to correlate sarcomeric protein expression with alterations in calcium cycling between the WT and gravin-t/t hearts. Gravin-t/t muscles had similar developed force compared to WT muscles despite having lower [Ca(2+)]i at any given external Ca(2+) concentration ([Ca(2+)]o). The time to peak force and peak [Ca(2+)]i were slower and the time to 75% relaxation was significantly prolonged in gravin-t/t muscles. Both Tf-interval and [Ca(2+)]i-interval relations were depressed in gravin-t/t muscles. Rf, however, did not change. Furthermore, Western blot analysis revealed decreased ryanodine receptor (RyR2) phosphorylation in gravin-t/t hearts. Gravin-t/t cardiac muscle exhibits increased force development in responsiveness to Ca(2+). The Ca(2+) cycling across the SR appears to be unaltered in gravin-t/t muscle. Our study suggests that gravin is an important component of cardiac contraction regulation via increasing myofilament sensitivity to calcium. Further elucidation of the mechanism can provide insights to role of gravin if any in the pathophysiology of impaired contractility. |
