DCM Mutations Alter Intracellular Ca2+ and Signaling

What can three mutations in thin filament regulatory proteins associated with dilated cardiomyopathy tell us about the highly variable phenotypes of DCM? Listen as Associate Editor Crystal Ripplinger (University of California Davis) interviews lead author Paul Robinson (University of Oxford) and expert Michael Greenberg (Washington University in St. Louis) about the latest work by Robinson and co-authors. By studying functional changes in cardiomyocyte contraction, calcium handling and signaling, Robinson and co-authors hoped to identify common pathway activations in troponin T, troponin I and tropomyosin mutations. Why did the authors opt to study DCM mutations in guinea pig cardiomyocytes rather than in a mouse model? Given the substantial number of mutations in both pediatric and adult-onset DCM, what are the implications here for precision medicine in the treatment of this disease? Listen to learn more.

 

Paul Robinson, Alexander J. Sparrow, Suketu Patel, Marta Malinowska, Svetlana N. Reilly, Yin-Hua Zhang, Barbara Casadei, Hugh Watkins, Charles Redwood Dilated cardiomyopathy mutations in thin-filament regulatory proteins reduce contractility, suppress systolic Ca2+, and activate NFAT and Akt signaling Am J Physiol Heart Circ Physiol, published July 21, 2020. DOI: doi.org/10.1152/ajpheart.00272.2020