Depression of Sarcolemmal Phospholipase C Activity in Congestive Heart Failure
The bioactivc phospholipids of the cardiac cell membrane (sarcolemma) and their signaling pathways are emerging as important mediators of the myocardial response to external stimuli, including catecholamines . It is known that the activity of the sympathetic nervous system is increased in congestive heart failure; this results in elevated levels of plasma catecholamines, which downregulate the β-adrenoceptors in failing hearts, leading to subsensitivity of the β-agonist-mediated biochemical and mechanical responses . The α1-adrenoceptors, which are associated with the positive inotropic effect of catecholamines via activation of the membranal phosphoinositide-phospholipase C (PLC) , were found to remain unchanged  or to increase [4,5] in heart failure. In view of the downregulation of the β-adrenoceptors, the α1 type reflects a greater proportion of the total adrenoceptor population in the failing ventricle [3–5]. Thus α1-adrenoceptors can be seen to play a dominant role in eliciting the positive inotropic action of catecholamines in failing heart .
KeywordsCongestive Heart Failure Positive Inotropic Effect Sarcolemmal Membrane Positive Inotropic Action Cardiac Cell Membrane
Unable to display preview. Download preview PDF.
- 1.Lamcrs JMJ, De Jongc HW, Panagia V, Van Heugten HAA. 1993. Receptor-mediated signalling pathways acting through hydrolysis of membrane phospholipids in cardiomyocytes. Cardioscience 4:121–131.Google Scholar
- 4.Dixon IMC, Dhalla NS. 1991. Alterations in cardiac adrenoceptors in congestive heart failure secondary to myocardial infarction. Cor Art Dis 2:805–814.Google Scholar
- 5.Vago T, Bevilacqua M, Norbiato G, Baldi G, Chebat E, Bertora P, Baroldi G, Accinni R. 1989. Identification of α1-adrenergic receptors on sarcolemma from normal subjects and patients with idiopathic dilated cardiomyopathy: Characteristics and linkage to GTP-binding protein. Circ Res 64:474–481.PubMedGoogle Scholar
- 8.Pucéat M, Hilal-Dandan R, Strulovici B, Brunton LL, Brown JH. 1994. Differential regulation of protein kinase C isoforms in isolated and adult rat cardiomyocytes. J Biol Chem 24:16938–16944.Google Scholar
- 13.Cockroft S, Thomas GMH. 1992. Inositol-lipid-specific phospholipase C isoenzymes and their differential regulation by receptors. Biochem J 288:1–14.Google Scholar
- 17.Pitts BJR. 1979. Stoichiometry of sodium-calcium exchange in cardiac sarcolemmal vesicles. J Biol Chem 245:6232–6235.Google Scholar
- 22.Wu D, Katz A, Lee C-H, Simon MI. 1993. Activation of phospholipase C by α1-adrenergic receptors is modified by the α subunits of Gq family. J Biol Chem 267:25798–25802.Google Scholar
- 25.Dhalla NS, Yates JC, Naimark B, Dhalla KS, Beamish RE, Ostadal B. 1992. Cardiotoxicity of catecholamines and related agents. In: Acosta D Jr, ed. Cardiovascular Toxicology, 2nd ed. New York: Raven Press, pp 239–282.Google Scholar