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Ventricular hypertrophy induced by mineralocorticoid treatment or aortic stenosis differentially regulates the expression of cardiac K+ channels in the rat

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Abstract

Rats treated with DOCA salts and subjected to abdominal aortic stenosis display left ventricle hypertrophy associated with a decrease in cardiac Ito current density and prolongation of the action potential duration. We investigated the molecular basis of these electrophysiological defects by analyzing the amount of mRNA corresponding to the genes encoding the α subunits of the left ventricle K+ channel at the steady state. The mRNAs corresponding to the α subunits of the K+ channel (Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3) were measured by quantitative RT-PCR using a specific Kv internal standard. In control rats, the Kv1.5 gene was only expressed at a low level, whereas the Kv4.2 and Kv4.3 genes were expressed at a high level. Regardless of the etiology of the hypertrophy, the amounts of Kv1.4 and Kv1.5 mRNA were similar in treated, sham and control rats. The amounts of Kv1.2 and Kv2.1 mRNA were markedly lower in DOCA-salt treated rats (66%) than in sham-DOCA rats, but no effect was observed after stenosis. The very conservative Kv4.2 and Kv4.3 genes were found to be downregulated simultaneously in both type of hypertrophy. However, the steady-state amount of Kv4 mRNA was even lower in rats with DOCA-salt-induced hypertrophy than in those with stenosis-induced ventricular hypertrophy. Therefore, the decrease in Ito density, consecutively to pressure- and volume-overload, is due to a large decrease in the amount of Kv4.2 and Kv4.3 mRNA. In addition, DOCA-salt treatment alters the amounts of Kv transcripts independently to cardiac hypertrophy, suggesting that the mineralocorticoid may be involved in Kv gene expression.

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References

  1. Swynghedauw B, Coraboeuf E: In: Cardiac Hypertrophy and Failure. Basic Aspects. Livingstone, 1995

  2. Benitah JP, Gomez AM, Bailly P, Da Ponte JP, Berson G, Delgado C, Lorente P: Heterogeneity of the early outward current in ventricular cells isolated from normal and hypertrophied rat hearts. J Physiol (Lond) 469: 111–138, 1993

    Google Scholar 

  3. Tomita F, Bassett AL, Myerburg RJ, Kimura S: Diminished transient outward currents in rat hypertrophied ventricular myocytes. Circ Res 75: 296–303, 1994

    Google Scholar 

  4. Coulombe A, Momtaz A, Richer P, Swynghedauw B, Coraboeuf E: Reduction of calcium-independent transient outward potassium current density in DOCA salt hypertrophied rat ventricular myocytes. Pflügers Arch 427: 47–55, 1994

    Google Scholar 

  5. Potreau D, Gomez JP, Fares N: Depressed transient outward current in single hypertrophied cardiomyocytes isolated from the right ventricle of ferret heart. Cardiovasc Res 30: 440–448, 1995

    Google Scholar 

  6. Qin D, Zhang ZH, Caref EB, Boutjdir M, Jain P, el-Sherif N: Cellular and ionic basis of arrhythmias in postinfarction remodeled ventricular myocardium. Circ Res 79: 461–473, 1996

    Google Scholar 

  7. Cerbai E, Barbieri M, Li Q, Mugelli A: Ionic basis of action potential prolongation of hypertrophied cardiac myocytes isolated from hypertensive rats of different ages. Cardiovasc Res 28: 1180–1187, 1994

    Google Scholar 

  8. Brooksby P, Levi AJ, Jones JV: The electrophysiological characteristics of hypertrophied ventricular myocytes from the spontaneously hypertensive rat. J Hypertens 11: 611–622, 1993

    Google Scholar 

  9. Rials SJ, Xu X, Wu Y, Marinchak RA, Kowey PR: Regression of LV hypertrophy with captopril normalizes membrane currents in rabbits. Am J Physiol 275: H1216–H1224, 1998

    Google Scholar 

  10. Li Q, Keung EC: Effects of myocardial hypertrophy on transient outward current. Am J Physiol 266: H1738–H1745, 1994

    Google Scholar 

  11. Ten Eick RE, Zhang K, Harvey RD, Bassett AL: Enhanced functional expression of transient outward current in hypertrophied feline myocytes. Cardiovasc Drugs Ther 7(suppl 3): 611–619, 1993

    Google Scholar 

  12. Serodio P, Vega-Saenz de Miera E, Rudy B: Cloning of a novel component of A-type K+ channels operating at subthreshold potentials with unique expression in heart and brain. J Neurophysiol 75: 2174–2179, 1996

    Google Scholar 

  13. Dixon JE, Shi W, Wang HS, McDonald C, Yu H, Wymore RS, Cohen IS, McKinnon D: Role of the Kv4.3 K+ channel in ventricular muscle. A molecular correlate for the transient outward current (published erratum appears in Circ Res 1997 Jan;80(1):147). Circ Res 79: 659–668, 1996

    Google Scholar 

  14. Yeola SW, Snyders DJ: Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current. Cardiovasc Res 33: 540–547, 1997

    Google Scholar 

  15. Feng J, Wible B, Li GR, Wang Z, Nattel S: Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes. Circ Res 80: 572–579, 1997

    Google Scholar 

  16. Bou-Abboud E, Nerbonne JM: Molecular correlates of the calcium-independent, depolarization-activated K+ currents in rat atrial myocytes. J Physiol (Lond) 517: 407–420, 1999

    Google Scholar 

  17. Matsubara H, Suzuki J, Inada M: Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy. J Clin Invest 92: 1659–1666, 1993

    Google Scholar 

  18. Gidh-Jain M, Huang B, Jain P, el-Sherif N: Differential expression of voltage-gated K+ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction. Circ Res 79: 669–675, 1996

    Google Scholar 

  19. Takimoto K, Li D, Hershman KM, Li P, Jackson EK, Levitan ES: Decreased expression of Kv4.2 and novel Kv4.3 K+ channel subunit mRNAs in ventricles of renovascular hypertensive rats. Circ Res 81: 533–539, 1997

    Google Scholar 

  20. Yao JA, Jiang M, Fan JS, Zhou YY, Tseng GN: Heterogeneous changes in K currents in rat ventricles three days after myocardial infarction. Cardiovasc Res 44: 132–145, 1999

    Google Scholar 

  21. Nishiyama A, Kambe F, Kamiya K, Seo H, Toyama J: Effects of thyroid status on expression of voltage-gated potassium channels in rat left ventricle. Cardiovasc Res 40: 343–351, 1998

    Google Scholar 

  22. Shimoni Y, Fiset C, Clark RB, Dixon JE, McKinnon D, Giles WR: Thyroid hormone regulates postnatal expression of transient K+ channel isoforms in rat ventricle. J Physiol (Lond) 500: 65–73, 1997

    Google Scholar 

  23. Wickenden AD, Kaprielian R, Parker TG, Jones OT, Backx PH: Effects of development and thyroid hormone on K+ currents and K+ channel gene expression in rat ventricle. J Physiol (Lond) 504: 271–286, 1997

    Google Scholar 

  24. Takimoto K, Levitan ES: Glucocorticoid induction of Kv1.5 K+ channel gene expression in ventricle of rat heart. Circ Res 75: 1006–1013, 1994

    Google Scholar 

  25. Levitan ES, Hershman KM, Sherman TG, Takimoto K: Dexamethasone and stress upregulate Kv1.5 K+ channel gene expression in rat ventricular myocytes. Neuropharmacology 35: 1001–1006, 1996

    Google Scholar 

  26. Kohya T, Kimura S, Myerburg RJ, Bassett AL: Susceptibility of hypertrophied rat hearts to ventricular fibrillation during acute ischemia. J Mol Cell Cardiol 20: 159–168, 1988

    Google Scholar 

  27. Goodwin FJ, Knowlton AI, Laragh JH: Absence of renin suppression by deoxycorticosterone acetate in rats. Am J Physiol 216: 1476–1480, 1969

    Google Scholar 

  28. Morton JJ, Garcia del Rio C, Hughes MJ: Effect of acute vasopressin infusion on blood pressure and plasma angiotensin II in normotensive and DOCA-salt hypertensive rats. Clin Sci 62: 143–149, 1982

    Google Scholar 

  29. Momtaz A, Coulombe A, Richer P, Mercadier JJ, Coraboeuf E: Action potential and plateau ionic currents in moderately and severely DOCA-salt hypertrophied rat hearts. J Mol Cell Cardiol 28: 2511–2522, 1996

    Google Scholar 

  30. Callens-el Amrani F, Paolaggi F, Swynghedauw B: Remodelling of the heart in DOCA-salt hypertensive rats by propranolol and by an alpha-2 agonist, rilmenidine. J Hypertens 7: 947–954, 1989

    Google Scholar 

  31. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159, 1987

    Google Scholar 

  32. Higuchi R, Krummel B, Saiki RK: A general method of in vitro preparation and specific mutagenesis of DNA fragments: Study of protein and DNA interactions. Nucleic Acids Res 16: 7351–7367, 1988

    Google Scholar 

  33. Freeman WM, Walker SJ, Vrana KE: Quantitative RT-PCR: Pitfalls and potential. Biotechniques 26: 112–124, 1999

    Google Scholar 

  34. Kaab S, Dixon J, Duc J, Ashen D, Nabauer M, Beuckelmann DJ, Steinbeck G, McKinnon D, Tomaselli GF: Molecular basis of transient outward potassium current downregulation in human heart failure: A decrease in Kv4.3 mRNA correlates with a reduction in current density. Circulation 98: 1383–1393, 1998

    Google Scholar 

  35. Andreeva L, Heads R, Green CJ: Cyclophilins and their possible role in the stress response. Int J Exp Pathol 80: 305–315, 1999

    Google Scholar 

  36. Doyle V, Virji S, Crompton M: Evidence that cyclophilin-A protects cells against oxidative stress. Biochem J 341: 127–132, 1999

    Google Scholar 

  37. Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M: Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci USA 88: 10045–10048, 1991

    Google Scholar 

  38. Nicod L, Rodriguez S, Letang JM, Viollon-Abadie C, Jacqueson A, Berthelot A, Richert L: Antioxidant status, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities in livers from control and DOCA-salt hypertensive male Sprague Dawley rats. Mol Cell Biochem 203: 33–39, 2000

    Google Scholar 

  39. Roberds SL, Tamkun MM: Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart. Proc Natl Acad Sci USA 88: 1798–1802, 1991

    Google Scholar 

  40. Dixon JE, McKinnon D: Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats. Circ Res 75: 252–260, 1994

    Google Scholar 

  41. Clark RB, Bouchard RA, Salinas-Stefanon E, Sanchez-Chapula J, Giles WR: Heterogeneity of action potential waveforms and potassium currents in rat ventricle. Cardiovasc Res 27: 1795–1799, 1993

    Google Scholar 

  42. Nerbonne JM: Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium. J Physiol 525: 285–298, 2000

    Google Scholar 

  43. Zhang TT, Takimoto K, Stewart AF, Zhu C, Levitan ES: Independent regulation of cardiac kv4.3 potassium channel expression by angiotensin ii and phenylephrine. Circ Res 88: 476–482, 2001

    Google Scholar 

  44. de Champlain J, Eid H, Drolet G, Bouvier M, Foucart S: Peripheral neurogenic mechanisms in deoxycorticosterone acetate - salt hypertension in the rat. Can J Physiol Pharmacol 67: 1140–1145, 1989

    Google Scholar 

  45. Okada H, Suzuki H, Kanno Y, Saruta T: Effect of nonpeptide vasopressin receptor antagonists on developing, and established DOCAsalt hypertension in rats. Clin Exp Hypertens 17: 469–483, 1995

    Google Scholar 

  46. Schiffrin EL, Lariviere R, Li JS, Sventek P, Touyz RM: Endothelin-1 gene expression and vascular hypertrophy in DOCA-salt hypertension compared to spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 1(suppl): S188–S190, 1995

    Google Scholar 

  47. Delcayre C, Silvestre JS, Garnier A, Oubenaissa A, Cailmail S, Tatara E, Swynghedauw B, Robert V: Cardiac aldosterone production and ventricular remodeling. Kidney Int 57: 1346–1351, 2000

    Google Scholar 

  48. Lombes M, Farman N, Bonvalet JP, Zennaro M: Identification and role of aldosterone receptors in the cardiovascular system (in process citation). Ann Endocrinol (Paris) 61: 41–46, 2000

    Google Scholar 

  49. Ikeda U, Hyman R, Smith TW, Medford RM: Aldosterone-mediated regulation of Na+, K(+)-ATPase gene expression in adult and neonatal rat cardiocytes. J Biol Chem 266: 12058–12066, 1991

    Google Scholar 

  50. Benitah JP, Vassort G: Aldosterone upregulates Ca(2+) current in adult rat cardiomyocytes. Circ Res 85: 1139–1145, 1999

    Google Scholar 

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Capuano, V., Ruchon, Y., Antoine, S. et al. Ventricular hypertrophy induced by mineralocorticoid treatment or aortic stenosis differentially regulates the expression of cardiac K+ channels in the rat. Mol Cell Biochem 237, 1–10 (2002). https://doi.org/10.1023/A:1016518920693

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