Abstract
The sequence of molecular events in cardiac muscle that begins with the interaction of autonomic neurotransmitters with their receptors and result in such responses as altered contractility, rhythmicity and energy metabolism are beginning to be comprehensible. There are still considerable gaps of knowledge, but there are several working hypotheses which are being subjected to intense investigation. Antagonists that bind specifically and strongly to adrenergic and muscarinic receptors will allow the isolation and characterization of these receptors. This aspect of the molecular pharmacology of cardiac muscle will not be discussed here. An important problem that must be solved is that of the mechanism whereby receptor activation is coupled to the initiation of the sequence of reactions that alter contractile, ion transport and metabolic responses. There are several schemes, supported by varying amounts of evidence, of how these responses are mediated. The important messengers of mediation are: Ca++ in activation-contraction coupling and contraction itself, cyclic AMP (adenosine 3’: 5’ — monophosphate), as the mediator of adrenergic responses, and cyclic GMP (guanosine 3’: 5’ -monophosphate) as the mediator of cholinergic control of cardiac rhythm and contraction (Fig. 1).
The author’ s investigations were supported by a grant from the National Heart and Lung Institute, HL 12373.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Reuter H.: Localization of beta adrenergic receptors and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J. Physiol. (Lond.) 242, 429–451 (1974)
Sulakhe P. V., Drummond G. I.: Protein kinase-catalyzed phosphorylation of muscle sarcolemma. Arch. Biochem. 161, 448–455 (1974)
Beavo J. A., Bechtel P. J., Krebs E. G.: Mechanism of control for cAMP dependent protein kinase from skeletal muscle. Advanc. Cyclic Nucleotide Res. 5 241–251 (1975)
Rosen O. M., Erlichman, J.: Reversible phosphorylation of a cyclic 3’: 5’ AMP-dependent protein kinase from bovine cardiac muscle. J. biol. Chem. 250, 7788–7794 (1975)
Katz, A. M.: This symposium
Huang, M., Drummond, G. I.: Effect of adenosine on cyclic AMP in ventricular myocardium. Fed. Proc. 35, 424 (1976)
Hofmann, F., Beavo, J. A., Bechtel, J. A., Krebs, E. G. Comparison of adenosine 3’: 5’ monophosphate-dependent protein kinases from rabbit skeletal and bovine heart muscle. J. biol. Chem. 250, 77957801 (1975)
Fischer, E. H., Becker, J. U., Blum, H. E., Byers, B., Heizman, C., Kerrick, G. W., Lehky, P., Malencik, D. A., Pocinwong, S.: Concerted regulation of glycogen metabolism and muscle contraction. In: 26th Colloquium-Mosbach 1975. Molecular Basis of Motility Heilmeyer, L., Ruegg, J. C., Wieland, Th. (eds.) Berlin-HeidelbergNew York: Springer-Verlag, pp. 137–158, 1976
Dobson, J. G., Jr., Ross, J. R. Jr., Mayer, S. E.: The role of cyclic AMP and calcium in contractility and glycogen phosphorylase activation in guinea pig papillary muscle. Circulat. Res. Accepted, for publication (1976)
Steinberg, D., Mayer, S. E., Khoo, J. C., Miller, E. A., Miller, R. E., Fredholm, B., Eichner, R. Hormonal regulation of lipase, phosphorylase and glycogen synthase in adipose tissue. Advanc. Cyclic Nucleotide Res. 5, 549–568 (1975)
Stull, J. T., Buss, J. E.: Phosphorylation of cardiac troponin by cyclic AMP-dependent protein kinase. Circulat. Res. Submitted for publication (1976)
Stull, J. T., Brostrom, C. O., Krebs, E. G.: Phosphorylation of the inhibitor component of troponin by phosphorylase kinase. J. biol. Chem. 247, 5272–5274 (1972)
Perrie, W. T., Smillie, L. B., Perrie, S. V.: A phosphorylated light chain component of myosin from skeletal muscle. Biochem. J. 135, 151–164 (1973)
Tsien, R. W.: Mode of action of chronotropic agents in cardiac Purkinje fibers. J. gen. Physiol. 64, 320–342 (1974)
Cohen, P.: The regulation of protein function by multisite phosphorylation. Trends biochem. Sci. L 38–40 (1976)
Killilea, S. D., Brandt, H., Lee, E. Y. C.: Modulation of protein function by phosphorylation: the role of protein phosphatase(s). Trends biochem. Sci. 1, 30–33 (1976)
Schultz, G., Hardman, J. G., Schultz, K., Baird, C. E., Sutherland, E. W.: The importance of calcium ions for the regulation of guanosine 3’: 5’ -cyclic monophosphate levels. Proc. nat. Acad. Sci. (Wash.) 70, 3889–3893 (1973)
Gross, S. R., Mayer, S. E.: Phosphorylase kinase mediating the effects of cyclic AMP in muscle. Metabolism 24, 369–380 (1975)
Dobson, J. G., Jr., Mayer, S. E.: Mechanism of activation of cardiac glycogen phosphorylase in ischemia and anoxia. Circulat. Res. 33, 412–430 (1973)
Drummond, G. I., Harwood, J. P., Powell, L. A.: Studies on the activation of phosphorylase in skeletal muscle by contraction and by epinephrine. J. biol. Chem. 246, 5716–5723 (1973)
Venter, J. L., Ross, J. R. Jr., Kaplan, N. O.: Lack of detectable change in cyclic AMP during the cardiac inotropic response to glass beads immobilized isoproterenol. Proc. nat. Acad. Sci. (Wash.) 72, 824–828 (1975)
Ingebretsen, W. R., Becker, E., Friedman, W. F., Mayer, S. E.: Contractile and biochemical responses of cardiac and skeletal muscle to isoproterenol covalently-linked to glass beads. Circulat. Res. Submitted for publication (1976)
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1977 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Mayer, S.E. (1977). Cyclic Nucleotides and Cardiac Contractility. In: Riecker, G., et al. Myocardial Failure. International Boehringer Mannheim Symposia. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-46352-5_11
Download citation
DOI: https://doi.org/10.1007/978-3-642-46352-5_11
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-08225-5
Online ISBN: 978-3-642-46352-5
eBook Packages: Springer Book Archive