Journal of Molecular and Cellular Cardiology
Volume 49, Issue 4 , Pages 639-646 , October 2010

Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts

  • Nathalie Gaborit

      Affiliations

    • INSERM, UMR915, l'institut du thorax, Nantes, F-44000 France
    • CNRS, ERL3147, Nantes, F-44000 France
    • Université de Nantes, Nantes, F-44000 France
  • ,
  • Andras Varro

      Affiliations

    • Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
    • Division for Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary
  • ,
  • Sabrina Le Bouter

      Affiliations

    • INSERM, UMR915, l'institut du thorax, Nantes, F-44000 France
    • CNRS, ERL3147, Nantes, F-44000 France
    • Université de Nantes, Nantes, F-44000 France
  • ,
  • Viktoria Szuts

      Affiliations

    • Division for Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary
  • ,
  • Denis Escande

      Affiliations

    • INSERM, UMR915, l'institut du thorax, Nantes, F-44000 France
    • CNRS, ERL3147, Nantes, F-44000 France
    • Université de Nantes, Nantes, F-44000 France
    • Deceased.
  • ,
  • Stanley Nattel

      Affiliations

    • Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, Montréal, Quebec, Canada
  • ,
  • Sophie Demolombe

      Affiliations

    • INSERM, UMR915, l'institut du thorax, Nantes, F-44000 France
    • CNRS, ERL3147, Nantes, F-44000 France
    • Université de Nantes, Nantes, F-44000 France
    • Corresponding Author InformationCorresponding author. IPMC, CNRS UMR6097, 660 route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France. Tel.: +33 4 93 95 77 51; fax: +33 4 93 95 77 08.

Received 30 March 2010 ,Revised 27 May 2010 ,Accepted 15 June 2010.

References 

  1. James AF, Choisy SC, Hancox JC. Recent advances in understanding sex differences in cardiac repolarization. Prog Biophys Mol Biol. 2007;94:265–319
  2. DeFranco DB. Regulation of steroid receptor subcellular trafficking. Cell Biochem Biophys. 1999;30:1–24
  3. Schram G, Pourrier M, Melnyk P, Nattel S. Differential distribution of cardiac ion channel expression as a basis for regional specialization in electrical function. Circ Res. 2002;90:939–950
  4. Antzelevitch C, Fish J. Electrical heterogeneity within the ventricular wall. Basic Res Cardiol. 2001;96:517–527
  5. Antzelevitch C, Brugada P, Brugada J, Brugada R, Towbin JA, Nademanee K. Brugada syndrome: 1992–2002: a historical perspective. J Am Coll Cardiol. 2003;41:1665–1671
  6. Gaborit N, Le Bouter S, Szuts V, Varro A, Escande D, Nattel S, et al. Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart. J Physiol. 2007;582:675–693
  7. Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, et al. Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart. J Physiol. 2005;562:223–234
  8. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–408
  9. Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998;95:14863–14868
  10. Zicha S, Xiao L, Stafford S, Cha TJ, Han W, Varro A, et al. Transmural expression of transient outward potassium current subunits in normal and failing canine and human hearts. J Physiol. 2004;561:735–748
  11. Dhamoon AS, Pandit SV, Sarmast F, Parisian KR, Guha P, Li Y, et al. Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+current. Circ Res. 2004;94:1332–1339
  12. Costantini DL, Arruda EP, Agarwal P, Kim KH, Zhu Y, Zhu W, et al. The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Cell. 2005;123:347–358
  13. Rosati B, Grau F, McKinnon D. Regional variation in mRNA transcript abundance within the ventricular wall. J Mol Cell Cardiol. 2006;40:295–302
  14. Liu XK, Katchman A, Drici MD, Ebert SN, Ducic I, Morad M, et al. Gender difference in the cycle length-dependent QT and potassium currents in rabbits. J Pharmacol Exp Ther. 1998;285:672–679
  15. James AF, Arberry LA, Hancox JC. Gender-related differences in ventricular myocyte repolarization in the guinea pig. Basic Res Cardiol. 2004;99:183–192
  16. Zicha S, Moss I, Allen B, Varro A, Papp J, Dumaine R, et al. Molecular basis of species-specific expression of repolarizing K+ currents in the heart. Am J Physiol (Heart Circ Physiol). 2003;285:H1641–H1649
  17. Drici MD, Baker L, Plan P, Barhanin J, Romey G, Salama G. Mice display sex differences in halothane-induced polymorphic ventricular tachycardia. Circulation. 2002;106:497–503
  18. Ranki HJ, Budas GR, Crawford RM, Jovanovic A. Gender-specific difference in cardiac ATP-sensitive K(+) channels. J Am Coll Cardiol. 2001;38:906–915
  19. Wettwer E, Amos GJ, Posival H, Ravens U. Transient outward current in human ventricular myocytes of subepicardial and subendocardial origin. Circ Res. 1994;75:473–482
  20. Nerbonne JM, Guo W. Heterogeneous expression of voltage-gated potassium channels in the heart: roles in normal excitation and arrhythmias. J Cardiovasc Electrophysiol. 2002;13:406–409
  21. Rosati B, Pan Z, Lypen S, Wang HS, Cohen I, Dixon JE, et al. Regulation of KChIP2 potassium channel beta subunit gene expression underlies the gradient of transient outward current in canine and human ventricle. J Physiol. 2001;533:119–125
  22. Guo W, Li H, Aimond F, Johns DC, Rhodes KJ, Trimmer JS, et al. Role of heteromultimers in the generation of myocardial transient outward K+currents. Circ Res. 2002;90:586–593
  23. Liu L, Fan QI, El-Zaru MR, Vanderpool K, Hines RN, Marsh JD. Regulation of DHP receptor expression by elements in the 5’-flanking sequence. Am J Physiol Heart Circ Physiol. 2000;278:H1153–H1162
  24. Kundu P, Ciobotaru A, Foroughi S, Toro L, Stefani E, Eghbali M. Hormonal regulation of cardiac KCNE2 gene expression. Mol Cell Endocrinol. 2008;292:50–62
  25. Borlak J, Thum T. Hallmarks of ion channel gene expression in end-stage heart failure. FASEB J. 2003;17:1592–1608
  26. Antzelevitch C, Brugada P, Brugada J, Brugada R, Shimizu W, Gussak I, et al. Brugada syndrome: a decade of progress. Circ Res. 2002;91:1114–1118
  27. Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P, et al. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation. 2002;106:2514–2519
  28. Di Diego JM, Cordeiro JM, Goodrow RJ, Fish JM, Zygmunt AC, Pérez GJ, et al. Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males. Circulation. 2002;106:2004–2011
  29. Antzelevitch C. Androgens and male predominance of the Brugada syndrome phenotype. Pacing Clin Electrophysiol. 2003;26:1429–1431
  30. Gaborit N, Wichter T, Varro A, Szuts V, Lamirault G, Eckardt L, et al. Transcriptional profiling of ion channel genes in Brugada syndrome and other right ventricular arrhythmogenic diseases. Eur Heart J. 2009;30:487–496
  31. Kyndt F, Probst V, Potet F, Demolombe S, Chevallier JC, Baro I, et al. Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family. Circulation. 2001;104:3081–3086
  32. Probst V, Allouis M, Sacher F, Pattier S, Babuty D, Mabo P, et al. Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation. J Cardiovasc Electrophysiol. 2006;17:270–275
  33. Roden DM. Taking the “idio” out of “idiosyncratic”: predicting torsades de pointes. Pacing Clin Electrophysiol. 1998;21:1029–1034
  34. Babiker FA, De Windt LJ, van Eickels M, Grohe C, Meyer R, Doevendans PA. Estrogenic hormone action in the heart: regulatory network and function. Cardiovasc Res. 2002;53:709–719
  35. Brower GL, Gardner JD, Janicki JS. Gender mediated cardiac protection from adverse ventricular remodeling is abolished by ovariectomy. Mol Cell Biochem. 2003;251:89–95
  36. Yang D, Song LS, Zhu WZ, Chakir K, Wang W, Wu C, et al. Calmodulin regulation of excitation–contraction coupling in cardiac myocytes. Circ Res. 2003;92:659–667
  37. Wu X, Chang B, Blair NS, Sargent M, York AJ, Robbins J, et al. Plasma membrane Ca2+-ATPase isoform 4 antagonizes cardiac hypertrophy in association with calcineurin inhibition in rodents. J Clin Invest. 2009;119:976–985
  38. Kadambi VJ, Ponniah S, Harrer JM, Hoit BD, Dorn GW, Walsh RA, et al. Cardiac-specific overexpression of phospholamban alters calcium kinetics and resultant cardiomyocyte mechanics in transgenic mice. J Clin Invest. 1996;97:533–539
  39. Kaab S, Näbauer M. Diversity of ion channel expression in health and disease. Eur Heart J Suppl. 2001;3:K31–K40
  40. Rosati B, McKinnon D. Regulation of ion channel expression. Circ Res. 2004;94:874–883
  41. Zhao XL, Gu DF, Qi ZP, Chen MH, Wei T, Li BX, et al. Comparative effects of sophocarpine and sophoridine on hERG K+ channel. Eur J Pharmacol. 2009;607:15–22
  42. Cheng AS, Jin VX, Fan M, Smith LT, Liyanarachchi S, Yan PS, et al. Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor-alpha responsive promoters. Mol Cell. 2006;21:393–404
  43. Sicouri S, Antzelevitch C. A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. Mol Cell Circ Res. 1991;68:1729–1741
  44. Akar FG, Yan GX, Antzelevitch C, Rosenbaum DS. Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome. Circulation. 2002;105:1247–1253
  45. Drici MD, Burklow TR, Haridasse V, Glazer RI, Woosley RL. Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Circulation. 1996;94:1471–1474

PII: S0022-2828(10)00242-7

doi: 10.1016/j.yjmcc.2010.06.005

Journal of Molecular and Cellular Cardiology
Volume 49, Issue 4 , Pages 639-646 , October 2010