Cardiac Ca2+ Channels and Sarcolemma Redox

  • Michael G. Clark
  • Stephen Rattigan
  • Perry J. F. Cleland
  • Stephen J. Edwards
  • Aidan G. M. Davison
Part of the NATO ASI Series book series (NSSA, volume 7)


Alpha-l-adrenergic receptors have been identified in both animal and human cardiac tissue (Schumann, 1978; Clark and Patten, 1984a; Bruckner et al., 1985) and several alpha adrenergic mediated events have been reported. Alpha agonists cause increases in inotropy of the heart (Bruckner et al., 1985) although this is not exclusive to alpha agonists as beta agonists also cause increases in inotropy and chronotropy. Alpha agonists also cause changes in metabolism such as activation of phosphofructokinase (Clark and Patten, 1984a) and increased glucose transport and uptake (Clark and Patten, 1984b; Rattigan et al., 1986; Abel et al., 1987), leading to increased glycolysis in the heart. Alpha stimulation has also been postulated to control hypertrophy of the heart (Simpson et al., 1986) and alpha agonists have been shown to cause the expression of c-myc and c-fos genes (Starksen et al., 1986; Barka et al., 1987).


Phorbol Ester Pertussis Toxin Beta Agonist Perfuse Heart Calcium Ionophore A23187 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abel, K.C., Rattigan, S. and Clark, M.G. (1988). Comparison of adrenergic agonist and insulin effects on 3–0-methyl D-glucose efflux and sarcolemmal cytochalasin B binding by perfused rat heart. Int. J. Biochem. 20, 291–295.PubMedCrossRefGoogle Scholar
  2. Avron,M. and Shavit, N. (1963). A sensitive and simple method for determination of ferrocyanide. Anal. Biochem. 6, 549–554.PubMedCrossRefGoogle Scholar
  3. Barka, T., van de Noen, H. and Shaw, P.A. (1987). Proto-oncogene fos (c-fos) expression ‘in the heart. Oncogene 1, 439–443.PubMedGoogle Scholar
  4. Berridge, M.J. (1982). A novel cellular signalling system based on the integration of phospholipid and calcium metabolism. In: Calcium and Cell Function Vol. III, pp. 1–36. Academic Press, New York.Google Scholar
  5. Berridge, M.J. (1987). Inositol lipids and cell proliferation. Biochem. Biophys. Acta 920, 301–305.CrossRefGoogle Scholar
  6. Blackmore, P.F. and Exton, J.H. (1986). Studies on the hepatic calcium-mobilizing activity of aluminium fluoride and glucagon. J. Biol. Chem. 261, 11056–11063.PubMedGoogle Scholar
  7. Bronner, C., Wiggins, C., Monte, D., Marki, F., Capron, A., Landry, Y. and Franson, R.C. (1987). Compound 48/80 is a potent inhibitor of phospholipase C and a dual modulator of phospholipase A2 from human platelet. Biochem. Biophys. Acta 920, 301–305.PubMedCrossRefGoogle Scholar
  8. Brown, J.H., Bruxton, I.L. and Brunton, L.L. (1985). a1-Adrenergic and muscarinic cholinergic stimulation of phosphoinositide hydrolysis in adult rat cardiomyocytes. Circ. Res. 57, 532–537.PubMedCrossRefGoogle Scholar
  9. Brown, J.H. and Jones, L.G. (1987). Phosphatidyl inositol turnover in the heart. In: Phosphoinositides and receptor mechanisms ( Putney, J.W. ed.), pp. 245–270. Alan R. Liss Inc., New York.Google Scholar
  10. Bruckner, R., Mugge, A. and Scholz, H. (1985). Existence and functional role of a1-adrenoceptors in the mammalian heart. J. Mol. Cell. Cardiol. 17, 639–645.PubMedCrossRefGoogle Scholar
  11. Clark, M.G. and Patten, G.S. (1984a). Adrenergic control of phosphofructokinase and glycolysis in rat heart. Curr. Top. Cell. Reg. 23, 127–176.Google Scholar
  12. Clark, M.G. and Patten, G.S. (1984b). Adrenergic regulation of glucose metabolism in rat heart. A Ca2+-dependent mechanism mediated by both a-and 3-adrenergic receptors. J. Biol. Chem. 259, 15204–15211.PubMedGoogle Scholar
  13. Clark, M.G. and Rattigan, S. (1986). Alpha adrenergic receptor mechanism: biochemical events. J. Mol. Cell. Cardiol. 18 Suppl. 5, 69–77.CrossRefGoogle Scholar
  14. Corvera, S., Schwartz, K.R., Graham, R.M. and Garcia-Sainz, J.A. (1986). Phorbol esters inhibit a1-adrenergic effects and decrease the affinity of liver cell a1-adrenergic receptors for (-) epinephrine. J. Biol. Chem. 261, 520–526.PubMedGoogle Scholar
  15. Cotecchia, S., Leeb-Lunberg, L.M.F., Hagen, P-O., Lefkowitz, R.J. and Caron, M.C. (1985). Phorbol ester effects on ai-adrenoceptor binding and phosphatidylinositol metabolism in cultured vascular smooth muscle cells. Life Sci. 37, 2389–2398.PubMedCrossRefGoogle Scholar
  16. Crane, F.L., Sun, I.L., Clark, M.G., Grebing, C. and Low, H. (1985). Transplasma-membrane redox systems in growth and development. Biochem. Biophys. Acta 811, 233–264.PubMedCrossRefGoogle Scholar
  17. Davison, A.G.M., Cleland, P.J.F., Rattigan, S. and Clark, M.G. (1988). .Google Scholar
  18. Downes, C.P. and Michell, R.H. (1981). The polyphosphoinositide phospho- diesterase of erythrocyte membranes. Biochem. J. 198, 133–140.PubMedGoogle Scholar
  19. Evans, S.W. and Farrar, W.L. (1987). Interleukin 2 and diacylglycerol stimulate phosphorylation of 40S ribosomal S6 protein. J. Biol. Chem. 262, 4624–4630.PubMedGoogle Scholar
  20. Exton, J.H. (1985). Mechanisms involved in a-adrenergic phenomena. Am. J. Physiol. 248, E633–E647.PubMedGoogle Scholar
  21. Kaibuchi, K., Takai, Y., Sawamura, M., Hoshijima, M., Fujikiwa, T. and Nishizuka, Y. (1983). Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation. J. Biol. Chem. 258, 6701–6704.PubMedGoogle Scholar
  22. Kunos, G. and Ishac, E.J.N. (1987). Mechanism of inverse regulation of alphal-and beta-adrenergic receptors. Biochem. Pharmacol. 36, 1185–1191.PubMedCrossRefGoogle Scholar
  23. Leung, E., Johnson, C.I. and Woodcock, E.A. (1986). Stimulation of phosphatidylinositol metabolism in the heart. Clin. Exp. Pharm. Physiol. 13, 359–363.CrossRefGoogle Scholar
  24. Low, H., Crane, F.L., Partick, E.J., Patten, G.S. and Clark, M.G. (1984). Properties and regulation of a trans-plasma membrane redox system of perfused rat heart. Biochem. Biophys. Acta 804, 253–260.PubMedCrossRefGoogle Scholar
  25. Low, H., Crane, F.L., Partick, E.J. and Clark, M.G. (1985). a-Adrenergic stimulation of trans-sarcolemma electron efflux in perfused rat heart. Possible regulation of Ca2+-channels by a sarcolemma redox system. Biochem. Biophys. Acta 844, 142–148.PubMedCrossRefGoogle Scholar
  26. McMillan, M., Chernow, B. and Roth, B.L. (1986). Phorbol esters inhibit alphal-adrenergic receptor-stimulated phosphoinositide hydrolysis and contraction in rat aorta: evidence for a link between vascular contraction and phosphoinositide turnover. Biochem. Biophys. Res. Commun. 134, 970–974.PubMedCrossRefGoogle Scholar
  27. Navas, P., Sun, I.L., Morre, D.J. and Crane, F.L. (1986). Decrease of NADH concentration in HeLa cells in the presence of transferrin or ferricyanide. Biochem. Biophys. Res. Commun. 135, 110–115.PubMedCrossRefGoogle Scholar
  28. Nishizuka, Y. (1984). The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308, 693–698.PubMedCrossRefGoogle Scholar
  29. Orellana, S., Solski, P.A. and Brown, J.H. (1987). Guanosine 5’-0(thiotriphosphate)-dependent inositol trisphosphate formation in membranes is inhibited by phorbol ester and protein kinase C. J. Biol. Chem. 262, 1638–1643.PubMedGoogle Scholar
  30. Rattigan, S., Edwards, S.J., Hettiarachchi, M. and Clark, M.G. (1986). The effects of a-and ß-adrenergic agents, Ca2+ and insulin on 2-deoxyglucose uptake and phosphorylation in perfused rat heart. Biochem. Biophys. Acta 889, 225–235.PubMedCrossRefGoogle Scholar
  31. Rinaldi, M.L., Capony, J-P. and Demaille, J.G. (1982). The cyclic AMP-dependent modulation of cardiac sarcolemmal slow calcium channels. J. Mol. Cell. Cardiol. 14, 279–289.PubMedCrossRefGoogle Scholar
  32. Schmitz, W., Scholz, H., Scholz, J., Steinfath, M., Lohse, M., Puurunen, J. and Schwabe, U. (1987). Pertussis toxin does not inhibit the al-adrenoceptor-mediated effect on inositol phosphate production in the heart. Eur. J. Pharm. 134, 377–378.CrossRefGoogle Scholar
  33. Schumann, H.J., Wagner, J., Knorr, A., Reidemeister, J.C., Sadony, V. and Schramm, G. (1978). Demonstration in human atrial preparations of a-adrenoceptors mediating positive inotropic effects. Naun-Schm. Arch. Pharmacol. 302, 333–336.CrossRefGoogle Scholar
  34. Slivka, S.R. and Insel, P.A. (1987). al-Adrenergic receptor-mediated phosphoinositide hydrolysis and prostaglandin E2 formation in Madin-Darby canine kidney cells. J. Biol. Chem. 262, 4200–4207.PubMedGoogle Scholar
  35. Simpson, P., Bishopric, N., Coughlin, S., Karliner, J., Ordahl, C., Starksen, N., Taso, T., White, N. and Williams, L. (1986). Dual trophic effects of the alphal-adrenergic receptor in cultured neonatal rat heart muscle cells. J. Mol. Cell. Cardiol. 18 Suppl. 5, 45–58.CrossRefGoogle Scholar
  36. Starksen, N.F., Simpson, P.C., Bishopric, N., Coughlin, S.R., Lee, W.M.F., Escobedo, J.A. and Williams, L.T. (1986). Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression. Proc. Natl. Acad. Sci. 83, 8348–8350PubMedCrossRefGoogle Scholar
  37. Whipps, D.E., Armston, A.E., Pryor, H.J. and Halestrap, A.P. (1987). Effects of glucagon and Ca2+ on the metabolism of phosphatidylinositol 4-phosphate in isolated rat hepatocytes and plasma membranes. Biochem. J. 241, 835–845.PubMedGoogle Scholar
  38. Woodcock, E.A., White, B.S., Smith, I. and McLeod, J.K. (1987). Stimulation of phosphatidylinositol metabolism in the isolated, perfused rat heart. Circ. Res. 61, 625–631.PubMedCrossRefGoogle Scholar
  39. Woods, N.M., Cutherbertson, K.S.R. and Cobbold, P.H. (1987). Phorbolester-induced alterations of free calcium ion transients in single rat hepatocytes. Biochem. J. 246, 619–623.PubMedGoogle Scholar
  40. Yatani, A., Codina, J., Imoto, Y., Reeves, J.P., Birnbaumer, L. and Brown, A.M. (1987). A G protein directly regulates mammalian cardiac calcium channels. Science 238, 1288–1292.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Michael G. Clark
    • 1
  • Stephen Rattigan
    • 1
  • Perry J. F. Cleland
    • 1
  • Stephen J. Edwards
    • 1
  • Aidan G. M. Davison
    • 1
  1. 1.Department of BiochemistryUniversity of TasmaniaHobartAustralia

Personalised recommendations