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Modulation of the hepatocyte rough endoplasmic reticulum single chloride channel by nucleotide–Mg2+ interaction

  • Ion Channels, Receptors and Transporters
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Abstract

The effect of nucleotides on single chloride channels derived from rat hepatocyte rough endoplasmic reticulum vesicles incorporated into bilayer lipid membrane was investigated. The single chloride channel currents were measured in 200/50 mmol/l KCl cis/trans solutions. Adding 2.5 mM adenosine triphosphate (ATP) and adenosine diphosphate (ADP) did not influence channel activity. However, MgATP addition inhibited the chloride channels by decreasing the channel open probability (Po) and current amplitude, whereas mixture of Mg2+ and ADP activated the chloride channel by increasing the Po and unitary current amplitude. According to the results, there is a novel regulation mechanism for rough endoplasmic reticulum (RER) Cl channel activity by intracellular MgATP and mixture of Mg2+ and ADP that would result in significant inhibition by MgATP and activation by mixture of Mg2+ and ADP. These modulatory effects of nucleotide–Mg2+ complexes on chloride channels may be dependent on their chemical structure configuration. It seems that Mg–nucleotide–ion channel interactions are involved to produce a regulatory response for RER chloride channels.

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Abbreviations

HEPES:

4-(2-Hydroxyethyl) piperazine-1-ethanesulfonic acid N-(2-hydroxyethyl) piperazine-N′-(2-ethanesulfonic acid) potassium salt

RER:

Rough endoplasmic reticulum

mitoKATP :

Mitochondrial ATP-sensitive K+ channel

DIDS:

4,4′-Diisothiocyanatostilbene-2,2′-disulfonic acid

CFTR:

Cystic fibrosis transmembrane conductance regulator

VDAC:

Voltage-dependent anion channel

References

  1. Ashrafpour M, Eliassi A, Sauve R et al (2008) ATP regulation of a large conductance voltage-gated cation channel in rough endoplasmic reticulum of rat hepatocytes. Arch Biochem Biophys 471:50–56

    Article  PubMed  CAS  Google Scholar 

  2. Ballarin C, Sorgato MC (1995) An electrophysiological study of yeast mitochondria. Evidence for two inner membrane anion channels sensitive to ATP. J Biol Chem 270:19262–19268

    Article  PubMed  CAS  Google Scholar 

  3. Bégault B, Anagnostopoulos T, Edelman A (1993) ATP-regulated chloride conductance in endoplasmic reticulum (ER)-enriched pig pancreas microsomes. Biochim Biophys Acta 1152:319–327

    Article  PubMed  Google Scholar 

  4. Choudhary OP, Ujwal R, Kowallis W et al (2010) The electrostatics of VDAC: implications for selectivity and gating. J Mol Biol 396:580–592

    Article  PubMed  CAS  Google Scholar 

  5. Clark AG, Murray D, Ashley RH (1997) Single-channel properties of a rat brain endoplasmic reticulum anion channel. Biophys J 73:168–178

    Article  PubMed  CAS  Google Scholar 

  6. Colombini M (2004) VDAC: the channel at the interface between mitochondria and the cytosol. Mol Cell Biochem 256(257):107–115

    Article  PubMed  Google Scholar 

  7. De Marchi U, Basso E, Szabo I, Zoratti M (2006) Electrophysiological characterization of the cyclophilin D-deleted mitochondrial permeability transition pore. Mol Membr Biol 23:521–530

    Article  PubMed  Google Scholar 

  8. Dzeja P, Terzic A (2009) Adenylate kinase and AMP signaling networks: metabolic monitoring, signal communication and body energy sensing. Int J Mol Sci 10:1729–1772

    Article  PubMed  CAS  Google Scholar 

  9. Eizirik DL, Cardozo AL, Cnop M (2008) The role for endoplasmic reticulum stress in diabetes mellitus. Endo Rev 29:42–61

    Article  CAS  Google Scholar 

  10. Eliassi A, Garneau L, Roy G, Sauve R (1997) Characterization of a chloride-selective channel from rough endoplasmic reticulum membranes of rat hepatocytes: evidence for a block by phosphate. J Membr Biol 159:219–229

    Article  PubMed  CAS  Google Scholar 

  11. Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140:900–917

    Article  PubMed  CAS  Google Scholar 

  12. Kan F, Jolicoeur WK, Paiment M (1992) Freeze-fracture analysis of the effects of intermediates of the phosphatidylinositol cycle on fusion of rough endoplasmic reticulum membranes. Biochim Biophys Acta 1107:331–341

    Article  PubMed  CAS  Google Scholar 

  13. Kawano T, Tanaka K, Equchi S et al (2010) Effects of ketamine on nicorandil induced ATP-sensitive potassium channel activity in cell line derived from rat aortic smooth muscle. J Med Invest 57:237–244

    Article  PubMed  Google Scholar 

  14. Ketchum CJ, Rajendrakumar GV, Maloney PC (2004) Characterization of adenosinetriphosphatase and transport activities of purified cystic fibrosis transmembrane conductance regulator. J Biochem 43:1045–1053

    Article  CAS  Google Scholar 

  15. Klitsch T, Siemen D (1991) Inner mitochondrial membrane anion channel is present in brown adipocytes but is not identical with the uncoupling protein. J Membr Biol 122:69–75

    Article  PubMed  CAS  Google Scholar 

  16. Kominkova V, Malekova L, Tomaskova Z et al (2010) Modulation of intracellular chloride channels by ATP and Mg2+. Biochim Biophys Acta 1797:1300–1312

    Article  PubMed  CAS  Google Scholar 

  17. Koszela PI, Choma K, Bednarczyk P et al (2007) Stilbene derivatives inhibit the activity of the inner mitochondrial membrane chloride channels. Cell Mol Biol Lett 12:493–508

    Article  Google Scholar 

  18. Kourie JI (1997) ATP-sensitive voltage- and calcium-dependent chloride channels in sarcoplasmic reticulum vesicles from rabbit skeletal muscle. J Membr Biol 157:39–51

    Article  PubMed  CAS  Google Scholar 

  19. Li X, Shimada K, Showalter LA, Weinman SA (2000) Biophysical properties of ClC-3 differentiate it from swelling activated chloride channels in chinese hamster ovary-K1 cells. J Biol Chem 275:35994–35998

    Article  PubMed  CAS  Google Scholar 

  20. Liu X, Luo M, Zhang L et al (2007) Bioelectric properties of chloride channels in human, pig, ferret, and mouse airway epithelia. Am J Respir Cell Mol Biol 36:313–323

    Article  PubMed  Google Scholar 

  21. Malekova L, Kominkova V, Ferko M et al (2007) Bongkrekic acid and atractyloside inhibits chloride channels from mitochondrial membranes of rat heart. Biochim Biophys Acta 1767:31–44

    Article  PubMed  CAS  Google Scholar 

  22. Malekova L, Krizanova O, Ondrias K (2009) H2S and HS− donor NaHS inhibits intracellular chloride channels. Gen Physiol Biophys 28:190–194

    Article  PubMed  CAS  Google Scholar 

  23. Malekova L, Tomaskova J, Novakova M et al (2007) Inhibitory effect of DIDS, NPPB, and phloretin on intracellular chloride channels. Pfl Arch Eur J Physiol 455:349–357

    Article  CAS  Google Scholar 

  24. O'Rourke B (2007) Mitochondrial ion channels. Annu Rev Physiol 69:19–49

    Article  PubMed  Google Scholar 

  25. Schmidt D, MacKinnon R (2008) Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane. Proc Natl Acad Sci 105:19275–19280

    Google Scholar 

  26. Sepehri H, Eliassi A, Sauve R, Ashrafpour M, Saghiri R (2007) Evidence for a large conductance voltage gated cationic channel in rough endoplasmic reticulum of rat hepatocytes. Arch Biochem Biophys 457:35–40

    Article  PubMed  CAS  Google Scholar 

  27. Singleton WS, Gray MS, Brown ML, White JL (1965) Chromatographically homogeneous lecithin from egg phospholipids. J Am Oil Chemists’ Soc 42:53–62

    Article  CAS  Google Scholar 

  28. Thevenod F, Gasser KW, Hopfer U (1990) Dual modulation of chloride conductance by nucleotides in pancreatic and parotid zymogen granules. Biochem J 272:119–126

    PubMed  CAS  Google Scholar 

  29. Thompson RJ, Nordeen MJ, Howel KE, Caldwell JH (2002) A large-conductance anion channel of the Golgi complex. Biophys J 83:278–289

    Article  PubMed  CAS  Google Scholar 

  30. Tomaskova Z, Ondrias K (2010) Mitochondrial chloride channels—what are they for? FEBS Lett 584:2085–2092

    Article  PubMed  CAS  Google Scholar 

  31. Wulff H (2008) New light on the “Old” chloride channel blocker DIDS. ACS Chem Biol 7:399–401

    Article  Google Scholar 

  32. Yamada H, Kawano T, Tanaka K et al (2007) Effects of intracellular MgADP and acidification on the inhibition of cardiac sarcolemmal ATP-sensitive potassium channels by propofol. J Anesth 21:472–479

    Article  PubMed  Google Scholar 

  33. Zeth K, Thein M (2010) Porins in prokaryotes and eukaryotes: common themes and variations. Biochem J 431:13–22

    Article  PubMed  CAS  Google Scholar 

  34. Zhang WK, Wang D, Duan Y et al (2010) Mechanosensitive gating of CFTR. Nat Cell Biol 12:507–512

    Article  PubMed  CAS  Google Scholar 

  35. Zhou JG, Ren JL, Qy Q et al (2005) Regulation of intracellular Cl concentration through volume regulated ClC-3 chloride channels in A10 vascular smooth muscle cells. J Biol Chem 280:7301–7308

    Article  PubMed  CAS  Google Scholar 

  36. Zingman LV, Alekseev AE, Hodgson ZDM, Terzic A (2007) ATP-sensitive potassium channels: metabolic sensing and cardioprotection. J Appl Physiol 103:1888–1893

    Article  PubMed  CAS  Google Scholar 

  37. Zoratti M, Marchi UD, Gulbins E, Szabò I (2009) Novel channels of the inner mitochondrial membrane. Biochim Biophys Acta 1787:351–363

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by a grant from the Cellular and Molecular Research Center of Babol University of Medical Sciences in collaboration with Neuroscience Research Center of Shahid Beheshti Medical Sciences University. We thank Dr. A. Eliassi for her generous guides.

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Correspondence to M. Ashrafpour.

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Ashrafpour, M., Babaei, J.F., Saghiri, R. et al. Modulation of the hepatocyte rough endoplasmic reticulum single chloride channel by nucleotide–Mg2+ interaction. Pflugers Arch - Eur J Physiol 464, 175–182 (2012). https://doi.org/10.1007/s00424-012-1121-z

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  • DOI: https://doi.org/10.1007/s00424-012-1121-z

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