Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3840883 | Translational Research | 2010 | 8 Pages |
Abstract
α- and β-Adrenergic receptor agonists induce an inotropic response in the adult heart by promoting the phosphorylation of several regulatory proteins, including myosin-binding protein C (MyBP-C), cardiac troponin I (cTnI), and phospholamban (PLB). However, the adrenergic-induced phosphorylation of these proteins has not been characterized in the developing heart. Accordingly, we evaluated MyBP-C, cTnI, and PLB phosphorylation in cultured neonatal rat cardiomyocytes (NRCMs) after α- and β-receptor activation with phenylephrine and isoproterenol. α-Receptor stimulation increased, whereas β-receptor activation reduced MyBP-C phosphorylation. Isoelectric-focusing experiments indicated that the amount of monophosphorylated MyBP-C was sensitive to α-adrenergic activation, but diphosphorylated and triphosphorylated MyBP-C levels were largely unaffected. The phosphorylation of cTnI and PLB was consistent with the mechanism observed in adult hearts: α- and β-Receptor stimulation phosphorylated both proteins. For cTnI, the greatest difference associated with β-receptor activation was observed in the diphosphorylated state, whereas α-receptor activation was associated with a marked increase in the tetraphosphorylated protein and absence of the unphosphorylated state. Despite these apparent changes in cTnI and PLB phosphorylation, β-receptor activation failed to alter calcium transients in NRCMs. Collectively, these findings suggest that, unlike cTnI and PLB, MyBP-C and inotropy are not coupled to β-adrenergic stimulation in NRCMs. Therefore, cTnI and PLB probably play a more central role in modulating contractile function in NRCMs in response to catecholamines than does MyBP-C, and MyBP-C may have a structural role in stabilizing thick filament assembly rather than influencing cross-bridge formation in developing hearts.
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Authors
Robert S. Decker, Amy K. Rines, Sakie Nakamura, Tejaswitha J. Naik, J. Andrew Wassertsrom, Hossein Ardehali,