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Inhibition of a cardiac sarcoplasmic reticulum chloride channel by tamoxifen

  • Ion Channels, Receptors and Transporters
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Abstract

Anion and cation channels present in the sarcoplasmic reticulum (SR) are believed to be necessary to maintain the electroneutrality of SR membrane during Ca2+ uptake by the SR Ca2+ pump (SERCA). Here we incorporated canine cardiac SR ion channels into lipid bilayers and studied the effects of tamoxifen and other antiestrogens on these channels. A Cl− channel was identified exhibiting multiple subconductance levels which could be divided into two primary conductance bands. Tamoxifen decreases the time the channel spends in its higher, voltage-sensitive band and the mean channel current. The lower, voltage-insensitive, conductance band is not affected by tamoxifen, nor is a K+ channel present in the cardiac SR preparation. By examining SR Ca2+ uptake, SERCA ATPase activity, and SR ion channels in the same preparation, we also estimated SERCA transport current, SR Cl− and K+ currents, and the density of SERCA, Cl−, and K+ channels in cardiac SR membranes.

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References

  1. Misquitta CM, Sing A, Grover AK (1999) Control of sarcoplasmic/endoplasmic-reticulum Ca2+ pump expression in cardiac and smooth muscle. Biochem J 338(Pt 1):167–173

    Article  PubMed  CAS  Google Scholar 

  2. Stern MD (1992) Theory of excitation–contraction coupling in cardiac muscle. Biophys J 63(2):497–517

    PubMed  CAS  Google Scholar 

  3. Bers DM, Eisner DA, Valdivia HH (2003) Sarcoplasmic reticulum Ca2+ and heart failure: roles of diastolic leak and Ca2+ transport. Circ Res 93(6):487–490

    Article  PubMed  CAS  Google Scholar 

  4. MacLennan DH, Kranias EG (2003) Phospholamban: a crucial regulator of cardiac contractility. Nat Rev Mol Cell Biol 4(7):566–577

    Article  PubMed  CAS  Google Scholar 

  5. Zimniak P, Racker E (1978) Electrogenicity of Ca2+ transport catalyzed by the Ca2+-ATPase from sarcoplasmic reticulum. J Biol Chem 253(13):4631–4637

    PubMed  CAS  Google Scholar 

  6. Yu X et al (1993) H+ countertransport and electrogenicity of the sarcoplasmic reticulum Ca2+ pump in reconstituted proteoliposomes. Biophys J 64(4):1232–1242

    PubMed  CAS  Google Scholar 

  7. Yu X, Inesi G (1993) Effects of anions on the Ca2+, H+ and electrical gradients formed by the sarcoplasmic reticulum ATPase in reconstituted proteoliposomes. FEBS Lett 328(3):301–304

    Article  PubMed  CAS  Google Scholar 

  8. Tadini-Buoninsegni F et al (2006) Pre-steady state electrogenic events of Ca2+/H+ exchange and transport by the Ca2+-ATPase. J Biol Chem 281(49):37720–37727

    Article  PubMed  CAS  Google Scholar 

  9. Obara K et al (2005) Structural role of countertransport revealed in Ca(2+) pump crystal structure in the absence of Ca(2+). Proc Natl Acad Sci USA 102(41):14489–14496

    Article  PubMed  CAS  Google Scholar 

  10. Decrouy A et al (1996) Biochemical regulation of sarcoplasmic reticulum Cl− channel from human atrial myocytes: involvement of phospholamban. J Mol Cell Cardiol 28(4):767–780

    Article  PubMed  CAS  Google Scholar 

  11. Rousseau E, Roberson M, Meissner G (1988) Properties of single chloride selective channel from sarcoplasmic reticulum. Eur Biophys J 16(3):143–151

    Article  PubMed  CAS  Google Scholar 

  12. Tanifuji M, Sokabe M, Kasai M (1987) An anion channel of sarcoplasmic reticulum incorporated into planar lipid bilayers: single-channel behavior and conductance properties. J Membr Biol 99(2):103–111

    Article  PubMed  CAS  Google Scholar 

  13. Miller C (1978) Voltage-gated cation conductance channel from fragmented sarcoplasmic reticulum: steady-state electrical properties. J Membr Biol 40(1):1–23

    Article  PubMed  CAS  Google Scholar 

  14. Coronado R, Miller C (1980) Decamethonium and hexamethonium block K+ channels of sarcoplasmic reticulum. Nature 288(5790):495–497

    Article  PubMed  CAS  Google Scholar 

  15. Wang J, Best PM (1994) Characterization of the potassium channel from frog skeletal muscle sarcoplasmic reticulum membrane. J Physiol 477(Pt 2):279–290

    PubMed  CAS  Google Scholar 

  16. Rousseau E et al (1992) Reconstitution and regulation of cation-selective channels from cardiac sarcoplasmic reticulum. Mol Cell Biochem 114(1–2):109–117

    PubMed  CAS  Google Scholar 

  17. Kargacin ME et al (2000) Tamoxifen inhibits Ca2+ uptake by the cardiac sarcoplasmic reticulum. Pflugers Arch 440(4):573–579

    PubMed  CAS  Google Scholar 

  18. Dodds ML, Kargacin ME, Kargacin GJ (2001) Effects of anti-oestrogens and beta-estradiol on calcium uptake by cardiac sarcoplasmic reticulum. Br J Pharmacol 132(7):1374–1382

    Article  PubMed  CAS  Google Scholar 

  19. Saito A et al (1984) Preparation and morphology of sarcoplasmic reticulum terminal cisternae from rabbit skeletal muscle. J Cell Biol 99(3):875–885

    Article  PubMed  CAS  Google Scholar 

  20. Kargacin ME, Scheid CR, Honeyman TW (1988) Continuous monitoring of Ca2+ uptake in membrane vesicles with fura-2. Am J Physiol 255(5 Pt 1):C694–C698

    PubMed  CAS  Google Scholar 

  21. Kargacin ME, Kargacin GJ (1994) Methods for determining cardiac sarcoplasmic reticulum Ca2+ pump kinetics from fura 2 measurements. Am J Physiol 267(4 Pt 1):C1145–C1151

    PubMed  CAS  Google Scholar 

  22. Kargacin ME, Ali Z, Kargacin G (1998) Anti-phospholamban and protein kinase A alter the Ca2+ sensitivity and maximum velocity of Ca2+ uptake by the cardiac sarcoplasmic reticulum. Biochem J 331(Pt 1):245–249

    PubMed  CAS  Google Scholar 

  23. Meissner G (1974) Isolation of sarcoplasmic reticulum from skeletal muscle. Methods Enzymol 31(Pt A):238–246

    Article  PubMed  CAS  Google Scholar 

  24. Worsfold M, Peter JB (1970) Kinetics of calcium transport by fragmented sarcoplasmic reticulum. J Biol Chem 245(21):5545–5552

    PubMed  CAS  Google Scholar 

  25. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260(6):3440–3450

    PubMed  CAS  Google Scholar 

  26. Kargacin ME, Kargacin GJ (1995) Direct measurement of Ca2+ uptake and release by the sarcoplasmic reticulum of saponin permeabilized isolated smooth muscle cells. J Gen Physiol 106(3):467–484

    Article  PubMed  CAS  Google Scholar 

  27. Karon BS et al (1995) A continuous spectrophotometric assay for simultaneous measurement of calcium uptake and ATP hydrolysis in sarcoplasmic reticulum. Anal Biochem 227(2):328–333

    Article  PubMed  CAS  Google Scholar 

  28. Kargacin GJ et al (2001) Iodide and bromide inhibit Ca(2+) uptake by cardiac sarcoplasmic reticulum. Am J Physiol Heart Circ Physiol 280(4):H1624–H1634

    PubMed  CAS  Google Scholar 

  29. Lytton J, Westlin M, Hanley MR (1991) Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps. J Biol Chem 266(26):17067–17071

    PubMed  CAS  Google Scholar 

  30. Miller C, Racker E (1976) Ca+-induced fusion of fragmented sarcoplasmic reticulum with artificial planar bilayers. J Membr Biol 30(3):283–300

    PubMed  CAS  Google Scholar 

  31. Ahern GP, Junankar PR, Dulhunty AF (1994) Single channel activity of the ryanodine receptor calcium release channel is modulated by FK-506. FEBS Lett 352(3):369–374

    Article  PubMed  CAS  Google Scholar 

  32. Kawano S et al (1992) Cardiac sarcoplasmic reticulum chloride channels regulated by protein kinase A. Circ Res 71(3):585–589

    PubMed  CAS  Google Scholar 

  33. Barry PH (1994) JPCalc, a software package for calculating liquid junction potential corrections in patch-clamp, intracellular, epithelial and bilayer measurements and for correcting junction potential measurements. J Neurosci Methods 51(1):107–116

    Article  PubMed  CAS  Google Scholar 

  34. Sachs F, Neil J, Barkakati N (1982) The automated analysis of data from single ionic channels. Pflugers Arch 395(4):331–340

    Article  PubMed  CAS  Google Scholar 

  35. Picher M, Decrouy A, Rousseau E (1996) Conducting and voltage-dependent behaviors of potassium ion channels reconstituted from diaphragm sarcoplasmic reticulum: comparison with the cardiac isoform. Biochim Biophys Acta 1279(1):93–103

    Article  PubMed  Google Scholar 

  36. Kourie JI et al (1996) Characteristics of two types of chloride channel in sarcoplasmic reticulum vesicles from rabbit skeletal muscle. Biophys J 70(1):202–221

    PubMed  CAS  Google Scholar 

  37. Rousseau E (1989) Single chloride-selective channel from cardiac sarcoplasmic reticulum studied in planar lipid bilayers. J Membr Biol 110(1):39–47

    Article  PubMed  CAS  Google Scholar 

  38. Townsend C, Rosenberg RL (1995) Characterization of a chloride channel reconstituted from cardiac sarcoplasmic reticulum. J Membr Biol 147(2):121–136

    PubMed  CAS  Google Scholar 

  39. Franciolini F, Petris A (1990) Chloride channels of biological membranes. Biochim Biophys Acta 1031(2):247–259

    PubMed  CAS  Google Scholar 

  40. Franciolini F, Petris A (1992) Transport mechanisms in chloride channels. Biochim Biophys Acta 1113(1):1–11

    PubMed  CAS  Google Scholar 

  41. Schlichter LC et al (1990) A large, multiple-conductance chloride channel in normal human T lymphocytes. Pflugers Arch 416(4):413–421

    Article  PubMed  CAS  Google Scholar 

  42. Hals GD, Stein PG, Palade PT (1989) Single channel characteristics of a high conductance anion channel in “sarcoballs”. J Gen Physiol 93(3):385–410

    Article  PubMed  CAS  Google Scholar 

  43. Soejima M, Kokubun S (1988) Single anion-selective channel and its ion selectivity in the vascular smooth muscle cell. Pflugers Arch 411(3):304–311

    Article  PubMed  CAS  Google Scholar 

  44. Coleman HA, Parkington HC (1987) Single channel Cl− and K+ currents from cells of uterus not treated with enzymes. Pflugers Arch 410(4–5):560–562

    Article  PubMed  CAS  Google Scholar 

  45. Bosma MM (1989) Anion channels with multiple conductance levels in a mouse B lymphocyte cell line. J Physiol 410:67–90

    PubMed  CAS  Google Scholar 

  46. Decrouy A, Juteau M, Rousseau E (1995) Examination of the role of phosphorylation and phospholamban in the regulation of the cardiac sarcoplasmic reticulum Cl− channel. J Membr Biol 146(3):315–326

    PubMed  CAS  Google Scholar 

  47. Patlak JB, Gration KA, Usherwood PN (1979) Single glutamate-activated channels in locust muscle. Nature 278(5705):643–645

    Article  PubMed  CAS  Google Scholar 

  48. Patlak JB, Ortiz M, Horn R (1986) Opentime heterogeneity during bursting of sodium channels in frog skeletal muscle. Biophys J 49(3):773–777

    PubMed  CAS  Google Scholar 

  49. Hille B (2001) Ion channels of excitable membranes. Sinauer Associates, Sunderland, Massachusetts, USA

    Google Scholar 

  50. Zhang JJ et al (1994) Tamoxifen blocks chloride channels. A possible mechanism for cataract formation. J Clin Invest 94(4):1690–1697

    Article  PubMed  CAS  Google Scholar 

  51. Zhang JJ et al (1995) Lens opacification by antioestrogens: tamoxifen vs ICI 182,780. Br J Pharmacol 115(8):1347–1348

    PubMed  CAS  Google Scholar 

  52. Allen MC et al (1998) Inhibition of ligand-gated cation-selective channels by tamoxifen. Eur J Pharmacol 354(2–3):261–269

    PubMed  CAS  Google Scholar 

  53. Dick GM, Kong ID, Sanders KM (1999) Effects of anion channel antagonists in canine colonic myocytes: comparative pharmacology of Cl−, Ca2+ and K+ currents. Br J Pharmacol 127(8):1819–1831

    Article  PubMed  CAS  Google Scholar 

  54. He J et al (2003) Tamoxifen inhibits Na+ and K+ currents in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 285(2):H661–H668

    PubMed  CAS  Google Scholar 

  55. Sahebgharani M et al (2001) Volume-activated chloride currents in HeLa cells are blocked by tamoxifen but not by a membrane impermeant quaternary analogue. Cell Physiol Biochem 11(2):99–104

    Article  PubMed  Google Scholar 

  56. Mitchell CH et al (2000) Tamoxifen and ATP synergistically activate Cl− release by cultured bovine pigmented ciliary epithelial cells. J Physiol 525(Pt 1):183–193

    Article  PubMed  CAS  Google Scholar 

  57. Verrecchia F, Herve J (1997) Reversible inhibition of gap junctional communication by tamoxifen in cultured cardiac myocytes. Pflugers Arch 434(1):113–116

    Article  PubMed  CAS  Google Scholar 

  58. Custodio JB, Almeida LM, Madeira VM (1993) The anticancer drug tamoxifen induces changes in the physical properties of model and native membranes. Biochim Biophys Acta 1150(2):123–129

    Article  PubMed  CAS  Google Scholar 

  59. Custodio JB, Almeida LM, Madeira VM (1993) The active metabolite hydroxytamoxifen of the anticancer drug tamoxifen induces structural changes in membranes. Biochim Biophys Acta 1153(2):308–314

    Article  PubMed  CAS  Google Scholar 

  60. Labarca PP, Miller C (1981) A K+-selective, three-state channel from fragmented sarcoplasmic reticulum of frog leg muscle. J Membr Biol 61(1):31–38

    Article  PubMed  CAS  Google Scholar 

  61. Takeda K, Trautmann A (1984) A patch-clamp study of the partial agonist actions of tubocurarine on rat myotubes. J Physiol 349:353–374

    PubMed  CAS  Google Scholar 

  62. Hill JA Jr, Coronado R, Strauss HC (1989) Potassium channel of cardiac sarcoplasmic reticulum is a multi-ion channel. Biophys J 55(1):35–45

    Article  PubMed  CAS  Google Scholar 

  63. Feher JJ, Fabiato A (1990) Cardiac sarcoplasmic reticulum: calcium uptake and release. In: Langer G (ed) Calcium and the Heart. Raven Press, New York, pp 199–268; p 387

    Google Scholar 

  64. Bers DM (1991) Excitation–contraction coupling and cardiac contractile force. Kluwer Academic, Norwell, MA, USA, p 258

    Google Scholar 

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Acknowledgements

The authors thank Teresa Emmett and Dragana Ponjevic for technical assistance. This work was supported by the Heart and Stroke Foundation of Alberta/Northwest Territories, the Natural Sciences and Engineering Research Council of Canada, the Alberta Heritage Foundation for Medical Research, and The Canadian Institutes of Health Research.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada

    Sanja Beca, Evgeny Pavlov, Margaret E. Kargacin, Roozbeh Aschar-Sobbi, Robert J. French & Gary J. Kargacin

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  1. Sanja Beca
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  2. Evgeny Pavlov
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  3. Margaret E. Kargacin
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  4. Roozbeh Aschar-Sobbi
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  5. Robert J. French
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  6. Gary J. Kargacin
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Correspondence to Gary J. Kargacin.

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Robert J. French and Gary J. Kargacin contributed equally to the work reported in this manuscript.

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Beca, S., Pavlov, E., Kargacin, M.E. et al. Inhibition of a cardiac sarcoplasmic reticulum chloride channel by tamoxifen. Pflugers Arch - Eur J Physiol 457, 121–135 (2008). https://doi.org/10.1007/s00424-008-0510-9

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  • DOI: https://doi.org/10.1007/s00424-008-0510-9

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