Abstract
The roles of cyclic AMP, cyclic AMP-dependent protein kinase and the phosphorylation of specific proteins in the regulation of cardiac contractility are briefly reviewed. Criteria for determining whether changes in cyclic AMP and protein phosphorylation are involved in a physiological response are discussed. Although cyclic AMP-dependent phosphorylation of the voltage-operated Ca2− channel, phospholamban, troponin-I and C-protein have all been implicated in the response of the heart to inotropic agents which elevate cyclic AMP, none of these phosphorylations satisfy all of the criteria completely. Evidence is presented that there are compartments of cyclic AMP in heart which are coupled to different functional responses.
Similar content being viewed by others
Abbreviations
- cAMP:
-
3′,5′ cyclic adenosine monophosphate
- PDE:
-
cyclic nucleotide phosphodiesterase
- cA-PrK:
-
cAMP-dependent protein kinase
- SR:
-
sarcoplasmic reticulum
- PGE1 :
-
prostaglandin E1
- Tn-I:
-
troponin I
References
Sutherland EW, Robison A, Butcher RW: Some aspects of the biological role of adenosine 3′,5′monophosphate. Circulation 37: 279–306, 1968
Krebs EG, Beavo JA: Phosphorylation-dephosphorylation of enzymes. Ann Rev Biochem 48: 923–959, 1979
Tsien RW: Cyclic AMP and contractile activity in heart. Adv Cyclic Nucleotide Res 8: 363–420, 1977
Korth M, Engels J: Inotropic and electrophysiological effects of 8-subsituted cyclic AMP analoges on guinea-pig papillary muscle. Naunyn-Schmiedeberg's Arch Pharmacol 301: 77–85, 1987
Reeves ML, Leigh BK, England PJ: The identification of a new cyclic nucleotide phosphodiesterase actitivy in human and guinea-pig cardiac ventricle. Biochem J 241: 535–541, 1987
Evans DB: Modulation of cyclic AMP: Mechanism for positive inotropic action. J Cardiovasc Pharmacol 8 (Suppl. 9): S22-S29, 1986
Reeves ML, England PJ, Murray KJ: Compartments of cyclic AMP-dependent protein kinase in perfused guinea pig hearts. Biochem Soc Trans 15: 955–956, 1987
Kaumann AJ, Hall JA, Murray KJ, Wells FC, Brown MJ: A comparison of the effects of adrenaline and noradrenaline on human heart: the role of β1- and β2-adrenoceptors in the stimulation of adenylate cyclase and contractile force. Eur Heart J (in press)
Murray KJ, England PJ, Lynham JA, Mills D, Reeves ML: Measurement of cyclic-AMP-dependent protein kinase activity ratio in heart by use of a synthetic peptide. Biochem Soc Trans 16: 355, 1988
England PJ, Shahid M: Effects of forskolin on contractile responses and protein phosphorylation in isolated perfused rat heart. Biochem J 246: 687–695, 1987
Murray KJ, England PJ, Reeves ML: Positive inotropic actions of SK&F 94120 occur via a cyclic AMP-dependent mechanism: Activation of cAMP-protein kinase (Abstr.) Br J Pharmacol 92: 755 p, 1987
Brunton LL, Hayes JS, Mayer SE: Hormonally specific phosphorylation of cardiac troponin I and activation of glycogen phosphorylase. Nature 280: 78–80, 1979
England PJ: Phosphorylation of cardiac muscle contractile proteins. In: AJ Drake-Holland, MIM Noble (eds), Cardiac Metabolism. John Wiley & Sons Ltd., UK, 1983, pp 365–389
Garvey JL, Kranias EG, Solaro RJ: Phosphorylation of C-protein, troponin 1 and phospholamban in isolated rabbit hearts. Biochem J 249: 709–714, 1988
Schlender KK, Thysseril TJ, Hegazy MG: Calcium-dependent phosphorylation of bovine cardiac C-protein and phosphorylase kinase. Biochem Biophys Res Commun 155: 45–51,1988
Demaille JG, Pechere J: The control of contractility by protein phosphorylation. Adv Cyclic Nucleotide Res 15: 337–371,1983
Catterall WA, Seagar MJ, Takahashi M: Molecular properties of dihydropyridine-sensitive calcium channels in skeletal muscle. J Biol Chem 263: 3535–3538, 1988
Murphy BJ, Tuana BS: Photoaffinity labelling and phosphorylation of the dihydropyridine binding subunit of the voltage regulated calcium channel from rabbit heart sarcolemma. J Mol Cell Cardiol 20 (Suppl. IV): S39, 1988
Sperelakis N: Regulation of calcium slow channels of cardiac muscle by cyclic nucleotides and phosphorylation. J Mol Cell Cardiol 20 (Suppl. II): 75–105, 1988
Buxton ILO, Brunton LL: Compartments of cyclic AMP and protein kinase in mammalian cardiomyocytes. J Biol Chem 258: 10233–10239, 1983
Hayes JC, Bowling N, King KL, Boder GB: Evidence for the selective regulation of the phosphorylation of myocyte proteins by isoproterenol and prostaglandin E1. Biochim Biophys Acta 714: 136–142, 1982
Aass H, Skomedal T, Osnes J: Increases of cyclic AMP in subcellular fractions of rat heart muscle after β-adrenergic stimulation. J Mol Cell Cardiol 20 847–860, 1988
Rosenthal W, Hescheler J, Trautwein W, Schulz G: Control of voltage-dependent Ca2+ channels by G protein-coupled receptors. FASEB J 2: 2784–2790, 1988
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Murray, K.J., Reeves, M.L. & England, P.J. Protein phosphorylation and compartments of cyclic AMP in the control of cardiac contraction. Mol Cell Biochem 89, 175–179 (1989). https://doi.org/10.1007/BF00220772
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00220772