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. 1987 Jul;80(1):88–94. doi: 10.1172/JCI113068

Effect of thyroid hormone on slow calcium channel function in cultured chick ventricular cells.

D Kim, T W Smith, J D Marsh
PMCID: PMC442205  PMID: 2439547

Abstract

The hyperthyroid state is associated with increased myocardial contractility. To clarify responsible mechanisms, we examined the effects of thyroid hormone on slow Ca channels, beta-adrenergic receptors, transsarcolemmal 45Ca flux and cytosolic free calcium in cultured chick ventricular cells. Compared with cells grown without triiodothyronine (T3), cells grown in 10 nM T3 possessed 67% (P less than 0.05) more dihydropyridine 3H-PN200-110 binding sites, 24% (P less than 0.05) more beta-adrenergic antagonist 3H-CGP12177 binding sites, a 57% (P less than 0.05) greater nifedipine-sensitive initial 45Ca uptake rate, and a 31% (P less than 0.05) greater nifedipine-sensitive 45Ca uptake rate in response to BAY k 8644. Time-averaged mean intracellular free Ca concentration ([Ca]i) measured with fura-2, total protein content, and dissociation constant values for 3H-PN200-110 or 3H-CGP12177 binding was not significantly different in the two groups of cells. BAY k 8644 (1 microM) increased mean [Ca]i 2.85- or 2.16-fold in cells grown with or without 10 nM T3, respectively. l-Isoproterenol (1 microM) increased [Ca]i 1.53- or 1.28-fold in cells grown with or without 10 nM T3, respectively. We conclude that thyroid hormone augments transsarcolemmal Ca influx, at least in part via slow Ca channels associated with increased numbers of these channels. T3-treated cells appear to be more responsive to the effects of BAY k 8644 or isoproterenol on [Ca]i.

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Selected References

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  1. Barry W. H., Smith T. W. Mechanisms of transmembrane calcium movement in cultured chick embryo ventricular cells. J Physiol. 1982 Apr;325:243–260. doi: 10.1113/jphysiol.1982.sp014148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bean B. P. Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6388–6392. doi: 10.1073/pnas.81.20.6388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brooks I., Flynn S. B., Owen D. A., Underwood A. H. Changes in cardiac function following administration of thyroid hormones in thyroidectomised rats: assessment using the isolated working rat heart preparation. J Cardiovasc Pharmacol. 1985 Mar-Apr;7(2):290–296. doi: 10.1097/00005344-198503000-00014. [DOI] [PubMed] [Google Scholar]
  4. Buccino R. A., Spann J. F., Jr, Pool P. E., Sonnenblick E. H., Braunwald E. Influence of the thyroid state on the intrinsic contractile properties and energy stores of the myocardium. J Clin Invest. 1967 Oct;46(10):1669–1682. doi: 10.1172/JCI105658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carter W. J., van der Weijden Benjamin W. S., Faas F. H. Effect of thyroid hormone on protein turnover in cultured cardiac myocytes. J Mol Cell Cardiol. 1985 Sep;17(9):897–905. doi: 10.1016/s0022-2828(85)80103-6. [DOI] [PubMed] [Google Scholar]
  6. Conway G., Heazlitt R. A., Fowler N. O., Gabel M., Green S. The effect of hyperthyroidism on the sarcoplasmic reticulum and myosin ATPase of dog hearts. J Mol Cell Cardiol. 1976 Jan;8(1):39–51. doi: 10.1016/0022-2828(76)90092-4. [DOI] [PubMed] [Google Scholar]
  7. Crie J. S., Wakeland J. R., Mayhew B. A., Wildenthal K. Direct anabolic effects of thyroid hormone on isolated mouse heart. Am J Physiol. 1983 Nov;245(5 Pt 1):C328–C333. doi: 10.1152/ajpcell.1983.245.5.C328. [DOI] [PubMed] [Google Scholar]
  8. Curfman G. D., Crowley T. J., Smith T. W. Thyroid-induced alterations in myocardial sodium-potassium-activated adenosine triphosphatase, monovalent cation active transport, and cardiac glycoside binding. J Clin Invest. 1977 Mar;59(3):586–590. doi: 10.1172/JCI108675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davis P. J., Blas S. D. In vitro stimulation of human red blood cell Ca2+-ATPase by thyroid hormone. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1073–1080. doi: 10.1016/0006-291x(81)90728-2. [DOI] [PubMed] [Google Scholar]
  10. Ferry D. R., Goll A., Glossmann H. Differential labelling of putative skeletal muscle calcium channels by [3H]-nifedipine, [3H]-nitrendipine, [3H]-nimodipine and [3H]-PN 200 110. Naunyn Schmiedebergs Arch Pharmacol. 1983 Jul;323(3):276–277. doi: 10.1007/BF00497674. [DOI] [PubMed] [Google Scholar]
  11. Flink I. L., Rader J. H., Morkin E. Thyroid hormone stimulates synthesis of a cardiac myosin isozyme. Comparison of the two-two-dimensional electrophoretic patterns of the cyanogen bromide peptides of cardiac myosin heavy chains from euthyroid and thyrotoxic rabbits. J Biol Chem. 1979 Apr 25;254(8):3105–3110. [PubMed] [Google Scholar]
  12. Goodkind M. J., Dambach G. E., Thyrum P. T., Luchi R. J. Effect of thyroxine on ventricular myocardial contractility and ATPase activity in guinea pigs. Am J Physiol. 1974 Jan;226(1):66–72. doi: 10.1152/ajplegacy.1974.226.1.66. [DOI] [PubMed] [Google Scholar]
  13. Grossman W., Robin N. I., Johnson L. W., Brooks H. L., Selenkow H. A., Dexter L. The enhanced myocardial contractility of thyrotoxicosis. Role of the beta adrenergic receptor. Ann Intern Med. 1971 Jun;74(6):869–874. doi: 10.7326/0003-4819-74-6-869. [DOI] [PubMed] [Google Scholar]
  14. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  15. Hertel C., Staehelin M. Reappearance of beta-adrenergic receptors after isoproterenol treatment in intact C6-cells. J Cell Biol. 1983 Nov;97(5 Pt 1):1538–1543. doi: 10.1083/jcb.97.5.1538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hoh J. F., McGrath P. A., Hale P. T. Electrophoretic analysis of multiple forms of rat cardiac myosin: effects of hypophysectomy and thyroxine replacement. J Mol Cell Cardiol. 1978 Nov;10(11):1053–1076. doi: 10.1016/0022-2828(78)90401-7. [DOI] [PubMed] [Google Scholar]
  17. Kim D., Smith T. W. Effects of thyroid hormone on calcium handling in cultured chick ventricular cells. J Physiol. 1985 Jul;364:131–149. doi: 10.1113/jphysiol.1985.sp015735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kim D., Smith T. W. Effects of thyroid hormone on sodium pump sites, sodium content, and contractile responses to cardiac glycosides in cultured chick ventricular cells. J Clin Invest. 1984 Oct;74(4):1481–1488. doi: 10.1172/JCI111561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Klein I., Hong C. Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart. J Clin Invest. 1986 May;77(5):1694–1698. doi: 10.1172/JCI112488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kokubun S., Prod'hom B., Becker C., Porzig H., Reuter H. Studies on Ca channels in intact cardiac cells: voltage-dependent effects and cooperative interactions of dihydropyridine enantiomers. Mol Pharmacol. 1986 Dec;30(6):571–584. [PubMed] [Google Scholar]
  21. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  22. Libby P. Long-term culture of contractile mammalian heart cells in a defined serum-free medium that limits non-muscle cell proliferation. J Mol Cell Cardiol. 1984 Sep;16(9):803–811. doi: 10.1016/s0022-2828(84)80004-8. [DOI] [PubMed] [Google Scholar]
  23. Marsh J. D., Roberts D. J. Adenylate cyclase regulation in intact cultured myocardial cells. Am J Physiol. 1987 Jan;252(1 Pt 1):C47–C54. doi: 10.1152/ajpcell.1987.252.1.C47. [DOI] [PubMed] [Google Scholar]
  24. Morkin E., Flink I. L., Goldman S. Biochemical and physiologic effects of thyroid hormone on cardiac performance. Prog Cardiovasc Dis. 1983 Mar-Apr;25(5):435–464. doi: 10.1016/0033-0620(83)90004-x. [DOI] [PubMed] [Google Scholar]
  25. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  26. Nayler W. G., Merrillees N. C., Chipperfield D., Kurtz J. B. Influence of hyperthyroidism on the uptake and binding of calcium by cardiac microsomal fractions and on mitochondrial structure. Cardiovasc Res. 1971 Oct;5(4):469–482. doi: 10.1093/cvr/5.4.469. [DOI] [PubMed] [Google Scholar]
  27. Niizoe K., Ogawa K., Satake T. Long-term effects of triiodothyronine and thiouracil on myocardial beta-adrenergic receptor numbers and cyclic AMP concentration in rats. Jpn Circ J. 1984 May;48(5):508–514. doi: 10.1253/jcj.48.508. [DOI] [PubMed] [Google Scholar]
  28. Philipson K. D., Edelman I. S. Thyroid hormone control of Na+-K+-ATPase and K+-dependent phosphatase in rat heart. Am J Physiol. 1977 May;232(5):C196–C201. doi: 10.1152/ajpcell.1977.232.5.C196. [DOI] [PubMed] [Google Scholar]
  29. Renaud J. F., Méaux J. P., Romey G., Schmid A., Lazdunski M. Activation of the voltage-dependent Ca2+ channel in rat heart cells by dihydropyridine derivatives. Biochem Biophys Res Commun. 1984 Nov 30;125(1):405–412. doi: 10.1016/s0006-291x(84)80382-4. [DOI] [PubMed] [Google Scholar]
  30. Rengasamy A., Ptasienski J., Hosey M. M. Purification of the cardiac 1,4-dihydropyridine receptor/calcium channel complex. Biochem Biophys Res Commun. 1985 Jan 16;126(1):1–7. doi: 10.1016/0006-291x(85)90563-7. [DOI] [PubMed] [Google Scholar]
  31. Rodgers R. L., Black S., Katz S., McNeill J. H. Thyroidectomy of SHR: effects on ventricular relaxation and on SR calcium uptake activity. Am J Physiol. 1986 May;250(5 Pt 2):H861–H865. doi: 10.1152/ajpheart.1986.250.5.H861. [DOI] [PubMed] [Google Scholar]
  32. Rudinger A., Mylotte K. M., Davis P. J., Davis F. B., Blas S. D. Rabbit myocardial membrane Ca2+-adenosine triphosphatase activity: stimulation in vitro by thyroid hormone. Arch Biochem Biophys. 1984 Feb 15;229(1):379–385. doi: 10.1016/0003-9861(84)90165-6. [DOI] [PubMed] [Google Scholar]
  33. Sanford C. F., Griffin E. E., Wildenthal K. Synthesis and degradation of myocardial protein during the development and regression of thyroxine-induced cardiac hypertrophy in rats. Circ Res. 1978 Nov;43(5):688–694. doi: 10.1161/01.res.43.5.688. [DOI] [PubMed] [Google Scholar]
  34. Suko J. Alterations of Ca 2 uptake and Ca 2+ activated ATPase of cardiac sarcoplasmic reticulum in hyper- and hypothyroidism. Biochim Biophys Acta. 1971 Nov 12;252(2):324–327. doi: 10.1016/0304-4165(71)90013-4. [DOI] [PubMed] [Google Scholar]
  35. Suko J. The calcium pump of cardiac sarcoplasmic reticulum. Functional alterations at different levels of thyroid state in rabbits. J Physiol. 1973 Feb;228(3):563–582. doi: 10.1113/jphysiol.1973.sp010100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tsai J. S., Chen A. Effect of L-triiodothyronine on (--)3H-dihydroalprenolol binding and cyclic AMP response to (--)adrenaline in cultured heart cells. Nature. 1978 Sep 14;275(5676):138–140. doi: 10.1038/275138a0. [DOI] [PubMed] [Google Scholar]
  37. Wahler G. M., Sperelakis N. New Ca2+ agonist (Bay K 8644) enhances and induces cardiac slow action potentials. Am J Physiol. 1984 Aug;247(2 Pt 2):H337–H340. doi: 10.1152/ajpheart.1984.247.2.H337. [DOI] [PubMed] [Google Scholar]
  38. Williams L. T., Lefkowitz R. J., Watanabe A. M., Hathaway D. R., Besch H. R., Jr Thyroid hormone regulation of beta-adrenergic receptor number. J Biol Chem. 1977 Apr 25;252(8):2787–2789. [PubMed] [Google Scholar]

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