| First Author | Wright PT | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 2 | Pages | 459-469 |
| PubMed ID | 29642004 | Mgi Jnum | J:271645 |
| Mgi Id | MGI:6279084 | Doi | 10.1016/j.celrep.2018.03.053 |
| Citation | Wright PT, et al. (2018) Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in beta2AR-cAMP Responsiveness in Murine Hearts. Cell Rep 23(2):459-469 |
| abstractText | Cardiomyocytes from the apex but not the base of the heart increase their contractility in response to beta2-adrenoceptor (beta2AR) stimulation, which may underlie the development of Takotsubo cardiomyopathy. However, both cell types produce comparable cytosolic amounts of the second messenger cAMP. We investigated this discrepancy using nanoscale imaging techniques and found that, structurally, basal cardiomyocytes have more organized membranes (higher T-tubular and caveolar densities). Local membrane microdomain responses measured in isolated basal cardiomyocytes or in whole hearts revealed significantly smaller and more short-lived beta2AR/cAMP signals. Inhibition of PDE4, caveolar disruption by removing cholesterol or genetic deletion of Cav3 eliminated differences in local cAMP production and equilibrated the contractile response to beta2AR. We conclude that basal cells possess tighter control of cAMP because of a higher degree of signaling microdomain organization. This provides varying levels of nanostructural control for cAMP-mediated functional effects that orchestrate macroscopic, regional physiological differences within the heart. |
