Phosphorylation of troponin I and phospholamban during catecholamine stimulation of rabbit heart (original) (raw)

Nature volume 298, pages 182–184 (1982)Cite this article

Abstract

During adrenergic stimulation heart cells develop increased force and there is an increase in the rate of rise and fall of force. These changes are thought to be triggered by the binding of catecholamine to the β-receptor, which in turn signals alterations in membranes and the contracto-regulatory protein complex by multiple, coordinated mechanisms involving Ca2+, cyclic nucleotides and protein phosphorylation1,2. This view is supported by results of in vitro studies with cardiac myofibrils3,4 and vesicles of sarcoplasmic reticulum (SR)5–7 showing that these organelles have sites of protein phosphorylation that may act as effectors of the adrenergic signal giving rise to the altered twitch dynamics. Phosphorylation of troponin I (TnI), a regulatory protein of cardiac myofibrils, results in a decreased steady-state affinity of troponin (TnC) for Ca2+, an increase in the off rate for Ca2+ exchange with TnC8 and a rightward shift of the relationship between free Ca2+ and myofibrillar force9 or ATPase3,4. Phosphorylation of phospholamban, a regulatory protein of cardiac SR, increases the velocity of Ca2+ transport by SR vesicles, the affinity of the transport protein for Ca2+ and the turnover of elementary steps of the ATPase reaction5–7,10,11. Taken together, these findings support the hypothesis that the inotropic response of the heart to catecholamine stimulation involves phosphorylation of TnI and phospholamban. Yet, although it is known that TnI is phosphorylated during adrenergic stimulation of beating heart12–14 there has been no clear evidence that phospholamban is phosphorylated at the same time. We now report that during the peak of the inotropic response of the rabbit heart to perfusion with isoproterenol, there is simultaneous phosphorylation of TnI and an 11,000-molecular weight (_M_r) protein associated with SR, which is probably monomeric phospholamban.

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Authors and Affiliations

  1. Department of Pharmacology and Cell Biophysics and Department of Physiology, University of Cincinnati, College of Medicine, Cincinnati, Ohio, 45267, USA
    E. G. Kranias & R. J. Solaro

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  1. E. G. Kranias
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  2. R. J. Solaro
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Kranias, E., Solaro, R. Phosphorylation of troponin I and phospholamban during catecholamine stimulation of rabbit heart.Nature 298, 182–184 (1982). https://doi.org/10.1038/298182a0

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