Differential Expression and Functional Regulation of Delayed Rectifier Channels

  • M. Stengl
  • P. G. A. Volders
  • M. A. Vos
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 242)


The terms differential expression and functional regulation have broad meanings, which can overlap and be explained in several ways. In this chapter, functional regulation is considered an acute modulation of the system (delayed rectifier channels in this case) and as such it will be discussed. Differential expression, on the one hand, reflects heterogeneity of delayed rectifiers expression in myocytes from different regions of the healthy heart; on the other hand it can also mean an altered (usually decreased) expression in pathological conditions.


Ventricular Myocytes Delay Rectifier Potassium Current Delay Rectifier Current Chromanol 293B Endocardial Myocytes 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Noble D, Tsien RW. Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres. J Physiol 1969;200:205–31PubMedGoogle Scholar
  2. 2.
    Sanguinetti MC, Jurkiewicz NK. Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol 1990;96:195215Google Scholar
  3. 3.
    Veldkamp MW, van Ginneken AC, Opthof T, Bouman LN. Delayed rectifier channels in human ventricular myocytes. Circulation 1995;92:3497–504CrossRefPubMedGoogle Scholar
  4. 4.
    Liu DW, Antzelevitch C. Characteristics of the delayed rectifier current (IKr and IKs) in canine ventricular epicardial, midmyocardial, and endocardial myocytes. A weaker IKs contributes to the longer action potential of the M cell. Circ Res 1995;76:351–65CrossRefPubMedGoogle Scholar
  5. 5.
    Li GR, Feng J, Yue L, Carrier M, Nattel S. Evidence for two components of delayed rectifier K+ current in human ventricular myocytes. Circ Res 1996;78:689–96CrossRefPubMedGoogle Scholar
  6. 6.
    Salata JJ, Jurkiewicz NK, Jow B, Folander K, Guinosso PJ Jr, Raynor B, Swanson R, Fermini B. IK of rabbit ventricle is composed of two currents: evidence for IKs. Am J Physiol 1996;271:H2477–89Google Scholar
  7. 7.
    Virag L, lost N, Opincariu M, Szolnoky J, Szecsi J, Bogats G, Szenohradszky P, Varro A, Papp JG. The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes. Cardiovasc Res 2001;49:790–7CrossRefPubMedGoogle Scholar
  8. 8.
    Follmer CH, Colatsky TJ. Block of delayed rectifier potassium current, IK, by flecainide and E-4031 in cat ventricular myocytes. Circulation 1990;82:289–93CrossRefPubMedGoogle Scholar
  9. 9.
    Nerbonne JM. Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium. J Physiol 2000;525:285–98CrossRefPubMedGoogle Scholar
  10. 10.
    Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 1995;81:299–307CrossRefPubMedGoogle Scholar
  11. 11.
    Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA. MiRPI forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 1999;97:175–87CrossRefPubMedGoogle Scholar
  12. 12.
    Lengyel C, lost N, Virag L, Varro A, Lathrop DA, Papp JG. Pharmacological block of the slow component of the outward delayed rectifier current (I(Ks)) fails to lengthen rabbit ventricular muscle QT(c) and action potential duration. Br J Pharmacol 2001;132:101–10CrossRefPubMedGoogle Scholar
  13. 13.
    lost N, Virag L, Opincariu M, Szecsi J, Varro A, Papp JG. Delayed rectifier potassium current in undiseased human ventricular myocytes. Cardiovasc Res 1998;40:508–15CrossRefGoogle Scholar
  14. 14.
    Varro A, Balati B, lost N, Takacs J, Virag L, Lathrop DA, Csaba L, Talosi L, Papp JG. The role of the delayed rectifier component IKs in dog ventricular muscle and Purkinje fibre repolarization. J Physiol 2000;523:67–81CrossRefPubMedGoogle Scholar
  15. 15.
    Smith PL, Baukrowitz T, Yellen G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature 1996;379:833–6CrossRefPubMedGoogle Scholar
  16. 16.
    Yang T, Snyders DJ, Roden DM. Rapid inactivation determines the rectification and [K+]o dependence of the rapid component of the delayed rectifier K+ current in cardiac cells. Circ Res 1997;80:782–9CrossRefPubMedGoogle Scholar
  17. 17.
    Scamps F, Carmeliet E. Delayed K+ current and external K+ in single cardiac Purkinje cells. Am J Physiol 1989;257:C1086–92PubMedGoogle Scholar
  18. 18.
    Sanguinetti MC, Jurkiewicz NK. Lanthanum blocks a specific component of IK and screens membrane surface change in cardiac cells. Am J Physiol 1990;259:H1881–9PubMedGoogle Scholar
  19. 19.
    Carmeliet E, Mubagwa K. Antiarrhythmic drugs and cardiac ion channels: mechanisms of action. Prog Biophys Mol Biol 1998;70:1–72CrossRefPubMedGoogle Scholar
  20. 20.
    Jurkiewicz NK, Sanguinetti MC. Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent. Specific block of rapidly activating delayed rectifier K+ current by dofetilide. Circ Res 1993;72:75–83CrossRefPubMedGoogle Scholar
  21. 21.
    Gintant GA. Two components of delayed rectifier current in canine atrium and ventricle. Does IKs play a role in the reverse rate dependence of class III agents? Circ Res 1996;78:26–37CrossRefGoogle Scholar
  22. 22.
    Gintant GA. Characterization and functional consequences of delayed rectifier current transient in ventricular repolarization. Am J Physiol Heart Circ Physiol 2000;278:H806–17PubMedGoogle Scholar
  23. 23.
    Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G. K(V)LQT1 and IsK (minK) proteins associate to form the IKs cardiac potassium current. Nature 1996;384:78–80CrossRefPubMedGoogle Scholar
  24. 24.
    Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT. Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature 1996;384:80–3CrossRefPubMedGoogle Scholar
  25. 25.
    Tristani-Firouzi M, Sanguinetti MC. Voltage-dependent inactivation of the human K+ channel KvLQTI is eliminated by association with minimal K+ channel (minK) subunits. J Physiol 1998;510:37–45CrossRefPubMedGoogle Scholar
  26. 26.
    Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Shen J, Timothy KW, Vincent GM, de Jager T, Schwartz Pi, Toubin JA, Moss AJ, Atkinson DL, Landes GM, Connors TD, Keating MT. Positional cloning of a novel potassium channel gene: KVLQTI mutations cause cardiac arrhythmias. Nat Genet 1996;12:17–23CrossRefPubMedGoogle Scholar
  27. 27.
    Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT. Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat Genet 1997;17:338–40CrossRefPubMedGoogle Scholar
  28. 28.
    Wang W, Xia J, Kass RS. MinK-KvLQTI fusion proteins, evidence for multiple stoichiometries of the assembled IsK channel. J Biol Chem 1998;273:34069–74CrossRefPubMedGoogle Scholar
  29. 29.
    Volders PG, Sipido KR, Carmeliet E, Spatjens RL, Wellens HJ, Vos MA. Repolarizing K+ currents ITOI and IKs are larger in right than left canine ventricular midmyocardium. Circulation 1999;99:206–10CrossRefPubMedGoogle Scholar
  30. 30.
    Chinn K. Two delayed rectifiers in guinea pig ventricular myocytes distinguished by tail current kinetics. J Pharmacol Exp Ther 1993;264:553–60PubMedGoogle Scholar
  31. 31.
    Busch AE, Suessbrich H, Waldegger S, Sailer E, Greger R, Lang H, Lang F, Gibson KJ, Maylie JG. Inhibition of IKs in guinea pig cardiac myocytes and guinea pig IsK channels by the chromanol 293B. Pflugers Arch 1996;432:1094–6CrossRefPubMedGoogle Scholar
  32. 32.
    Salata JJ, Jurkiewicz NK, Sanguinetti MC, Siegl PKS, Claremon DC, Remy DC, Elliott JM, Libby BE. The novel class III antiarrhythmic agent L-735,821 is a potent and selective blocker of IKs in guinea pig ventricular myocytes. Circulation 1996;94:1–529CrossRefGoogle Scholar
  33. 33.
    Cordeiro JM, Spitzer KW, Giles WR. Repolarizing K+ currents in rabbit heart Purkinje cells. J Physiol 1998;508:811–23CrossRefPubMedGoogle Scholar
  34. 34.
    Selnick HG, Liverton NJ, Baldwin JJ, Butcher JW, Claremon DA, Elliott JM, Freidinger RM, King SA, Libby BE, McIntyre CJ, Pribush DA, Remy DC, Smith GR, Tebben AJ, Jurkiewicz NK, Lynch JJ, Salata JJ, Sanguinetti MC, Siegl PK, Slaughter DE, Vyas K. Class III antiarrhythmic activity in vivo by selective blockade of the slowly activating cardiac delayed rectifier potassium current IKs by (R)-2-(2,4-trifluoromethyl)-N-[2-oxo-5-phenyl-1-(2,2,2trifluoroethyl)- 2, 3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]acetamide. J Med Chem 1997;40:3865–8CrossRefPubMedGoogle Scholar
  35. 35.
    Gogelein H, Bruggemann A, Gerlach U, Brendel J, Busch AE. Inhibition of IKs channels by HMR 1556. Naunyn Schmiedebergs Arch Pharmacol 2000;362:480–8CrossRefPubMedGoogle Scholar
  36. 36.
    Sun ZQ, Thomas GP, Antzelevitch C. Chromanol 293B inhibits slowly activating delayed rectifier and transient outward currents in canine left ventricular myocytes. J Cardiovasc Electrophysiol 2001;12:472–8CrossRefPubMedGoogle Scholar
  37. 37.
    Fan Z, Hiraoka M. Depression of delayed outward K+ current by Co2+ in guinea pig ventricular myocytes. Am J Physiol 1991;261:C23–31PubMedGoogle Scholar
  38. 38.
    Bosch RF, Gaspo R, Busch AE, Lang HJ, Li GR, Nattel S. Effects of the chromanol 293B, a selective blocker of the slow, component of the delayed rectifier K+ current, on repolarization in human and guinea pig ventricular myocytes. Cardiovasc Res 1998;38:441–50CrossRefPubMedGoogle Scholar
  39. 39.
    Burashnikov A, Antzelevitch C. Block of I(Ks) does not induce early afterdepolarization activity but promotes beta-adrenergic agonist-induced delayed afterdepolarization activity. J Cardiovasc Electrophysiol 2000;11:458–65CrossRefPubMedGoogle Scholar
  40. 40.
    Shimizu W, Antzelevitch C. Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. J Am Coll Cardiol 2000;35:778–86CrossRefPubMedGoogle Scholar
  41. 41.
    Lynch JJ Jr, Houle MS, Stump GL, Wallace AA, Gilberto DB, Jahansouz H, Smith GR, Tebben AJ, Liverton NJ, Selnick HG, Claremon DA, Billman GE. Antiarrhythmic efficacy of selective blockade of the cardiac slowly activating delayed rectifier current, I(Ks), in canine models of malignant ischemic ventricular arrhythmia. Circulation 1999;100:1917–22CrossRefPubMedGoogle Scholar
  42. 42.
    Pham TV, Sosunov EA, Gainullin RZ, Danilo P Jr, Rosen MR. Impact of sex and gonadal steroids on prolongation of ventricular repolarization and arrhythmias induced by I(k)blocking drugs. Circulation 2001;103:2207–12CrossRefPubMedGoogle Scholar
  43. 43.
    Schreieck J, Wang Y, Gjini V, Korth M, Zrenner B, Schomig A, Schmitt C. Differential effect of beta-adrenergic stimulation on the frequency-dependent electrophysiologic actions of the new class III antiarrhythmics dofetilide, ambasilide, and chromanol 293B. J Cardiovasc Electrophysiol 1997;8:1420–30CrossRefPubMedGoogle Scholar
  44. 44.
    Han W, Wang Z, Nattel S. Slow delayed rectifier current and repolarization in canine cardiac Purkinje cells. Am J Physiol Heart Circ Physiol 2001;280:H1075–80PubMedGoogle Scholar
  45. 45.
    Sanguinetti MC, Jurkiewicz NK, Scott A, Siegl PK. Isoproterenol antagonizes prolongation of refractory period by the class Ill antiarrhythmic agent E-4031 in guinea pig myocytes. Mechanism of action. Circ Res 1991;68:77–84CrossRefPubMedGoogle Scholar
  46. 46.
    Sanguinetti MC, Jurkiewicz NK. Delayed rectifier outward K+ current is composed of two currents in guinea pig atrial cells. Am J Physiol 1991;260:H393–9PubMedGoogle Scholar
  47. 47.
    Heath BM, Terrar DA. Protein kinase C enhances the rapidly activating delayed rectifier potassium current, IKr, through a reduction in C-type inactivation in guinea-pig ventricular myocytes. J Physiol 2000;522:391–402CrossRefPubMedGoogle Scholar
  48. 48.
    Compton SJ, Lux RL, Ramsey MR, Strelich KR, Sanguinetti MC, Green LS, Keating MT, Mason JW. Genetically defined therapy of inherited long-QT syndrome. Correction of abnormal repolarization by potassium. Circulation 1996;94:1018–22CrossRefPubMedGoogle Scholar
  49. 49.
    Tan HL, Alings M, Van Olden RW, Wilde AA. Long-term (subacute) potassium treatment in congenital HERG-related long QT syndrome (LQTS2). J Cardiovasc Electrophysiol 1999;10:229–33CrossRefPubMedGoogle Scholar
  50. 50.
    Daleau P, Turgeon J. Angiotensin II modulates the delayed rectifier potassium current of guinea pig ventricular myocytes. Pflugers Arch 1994;427:553–5CrossRefPubMedGoogle Scholar
  51. 51.
    Rees SA, Vandenberg JI, Wright AR, Yoshida A, Powell T. Cell swelling has differential effects on the rapid and slow components of delayed rectifier potassium current in guinea pig cardiac myocytes. J Gen Physiol 1995;106:1151–70CrossRefPubMedGoogle Scholar
  52. 52.
    Walsh KB, Kass RS. Regulation of a heart potassium channel by protein kinase A and C. Science 1988;242:67–9CrossRefPubMedGoogle Scholar
  53. 53.
    Tohse N, Nakaya H, Kanno M. Alpha 1-adrenoceptor stimulation enhances the delayed rectifier K+ current of guinea pig ventricular cells through the activation of protein kinase C. Circ Res 1992;71:1441–6CrossRefPubMedGoogle Scholar
  54. 54.
    Varnum MD, Busch AE, Bond CT, Maylie J, Adelman JP. The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C. Proc Natl Acad Sci U S A 1993;90:11528–32CrossRefPubMedGoogle Scholar
  55. 55.
    Lo CF, Numann R. Independent and exclusive modulation of cardiac delayed rectifying K+ current by protein kinase C and protein kinase A. Circ Res 1998;83:995–1002CrossRefPubMedGoogle Scholar
  56. 56.
    Tohse N, Kameyama M, Irisawa H. Intracellular Ca2+ and protein kinase C modulate K+ current in guinea pig heart cells. Am J Physiol 1987;253:H1321–4PubMedGoogle Scholar
  57. 57.
    Nitta J, Furukawa T, Marumo F, Sawanobori T, Hiraoka M. Subcellular mechanism for Ca(2+)-dependent enhancement of delayed rectifier K+ current in isolated membrane patches of guinea pig ventricular myocytes. Circ Res 1994;74:96–104CrossRefPubMedGoogle Scholar
  58. 58.
    Washizuka T, Horie M, Watanuki M, Sasayama S. Endothelin-1 inhibits the slow component of cardiac delayed rectifier K+ currents via a pertussis toxin-sensitive mechanism. Circ Res 1997;81:211–8CrossRefPubMedGoogle Scholar
  59. 59.
    Groh WJ, Gibson KJ, Maylie JG. Hypotonic-induced stretch counteracts the efficacy of the class Ill antiarrhythmic agent E-4031 in guinea pig myocytes. Cardiovasc Res 1996;31:237–45PubMedGoogle Scholar
  60. 60.
    Volders PG, Sipido KR, Vos MA, Spatjens RL, Leunissen JD, Carmeliet E, Wellens HJ. Downregulation of delayed rectifier K(+) currents in dogs with chronic complete atrioventricular block and acquired torsades de pointes. Circulation 1999;100:2455–61CrossRefPubMedGoogle Scholar
  61. 61.
    Ramakers C, Doevedans PA, Vos MA, Antzelevitch C, Dumaine R. KCNQ1 and KCNEI expression is reduced in dogs with chronic AV block. Biophys J 2000;78:220AGoogle Scholar
  62. 62.
    Rose J, Zheng MQ, Juang G, Kong W, O’Rourke B, Tomaselli GF. Delayed rectifier current in heart failure: Depressed function without changes in protein expression or protein level. Circulation 1999;100:1–425CrossRefGoogle Scholar
  63. 63.
    Schultz JH, Volk T, Ehmke H. Heterogeneity of Kv2.l mRNA expression and delayed rectifier current in single isolated myocytes from rat left ventricle. Circ Res 2001;88:483–490CrossRefPubMedGoogle Scholar
  64. 64.
    Furukawa T, Kimura S, Furukawa N, Bassett AL, Myerburg RJ. Potassium rectifier currents differ in myocytes of endocardial and epicardial origin. Cire Res 1992;70:91–103CrossRefGoogle Scholar
  65. 65.
    Sicouri S, Antzelevitch C. A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. The M cell. Cire Res 1991;68:1729–41CrossRefGoogle Scholar
  66. 66.
    Brahmajothi MV, Morales MJ, Reimer KA, Strauss HC. Regional localization of ERG, the channel protein responsible for the rapid component of the delayed rectifier, K+ current in the ferret heart. Circ Res 1997;81:128–35CrossRefPubMedGoogle Scholar
  67. 67.
    Xu X, Rials SJ, Wu Y, Salata JJ, Liu T, Bharucha DB, Marinchak RA, Kowey PR. Left ventricular hypertrophy decreases slowly but not rapidly activating delayed rectifier potassium currents of epicardial and endocardial myocytes in rabbits. Circulation 2001;103:1585–90CrossRefPubMedGoogle Scholar
  68. 68.
    Cheng J, Kamiya K, Liu W, Tsuji Y, Toyama J, Kodama I. Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilideclass Ill agents. Cardiovasc Res 1999;43:135–47CrossRefPubMedGoogle Scholar
  69. 69.
    Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT. Spectrum of mutations in long-QT syndrome genes. KVLQTI, HERG, SCN5A, KCNEI, and KCNE2. Circulation 2000;102:1178–85CrossRefPubMedGoogle Scholar
  70. 70.
    Vos MA, de Groot SH, Verduyn SC, van der Zande J, Leunissen HD, Cleutjens JP, van Bilsen M, Daemen MJ, Schreuder JJ, Allessie MA, Wellens HJ. Enhanced susceptibility for acquired torsade de pointes arrhythmias in the dog with chronic, complete AV block is related to cardiac hypertrophy and electrical remodeling. Circulation 1998;98:1125–35CrossRefPubMedGoogle Scholar
  71. 71.
    van Opstal JM, Verduyn SC, Leunissen HD, de Groot SH, Wellens HJ, Vos MA. Electrophysiological parameters indicative of sudden cardiac death in the dog with chronic complete AV-block. Cardiovasc Res 2001;50:354–61CrossRefPubMedGoogle Scholar
  72. 72.
    Thomas GP, Vos MA, Antzelevitch C. The effect of volume overload hypertrophy on transmural distribution of the delayed rectifier (IK, and IKs) and transient outward (l) currents in the canine heart. Pace 2001;24:597Google Scholar
  73. 73.
    Sipido KR, Volders PG, de Groot SH, Verdonck F, Van de Werf F, Wellens HJ, Vos MA. Enhanced Ca(2+) release and Na/Ca exchange activity in hypertrophied canine ventricular myocytes: potential link between contractile adaptation and arrhythmogenesis. Circulation 2000;102:2137–44CrossRefPubMedGoogle Scholar
  74. 74.
    Li GR, Sun H, Nattel S. Action potential and ionic remodeling in a dog model of heart failure. Pace 1998a;21:877 (abstract)Google Scholar
  75. 75.
    Li GR, Sun H, Feng J, Nattel S. Ionic mechanisms of the action potential prolongation in failing human ventricular cells. Pace 1998b;21:877Google Scholar
  76. 76.
    Jiang M, Cabo C, Yao J, Boyden PA, Tseng G. Delayed rectifier K currents have reduced amplitudes and altered kinetics in myocytes from infarcted canine ventricle. Cardiovasc Res 2000;48:34–43CrossRefPubMedGoogle Scholar
  77. 77.
    Gillis AM, Geonzon RA, Mathison HJ, Kulisz E, Lester WM, Duff HJ. The effects of barium, dofetilide and 4-aminopyridine on ventricular repolarization in normal and hypertrophied rabbit heart. J Pharmacol Exp Ther 1998;285: 262–270PubMedGoogle Scholar
  78. 78.
    Tsuji Y, Opthof T, Kamiya K, Yasui K, Liu W, Lu Z, Kodama I I. Pacing-induced heart failure causes a reduction of delayed rectifier potassium currents along with decreases in calcium and transient outward currents in rabbit ventricle. Cardiovasc Res 2000;48:300–9CrossRefPubMedGoogle Scholar
  79. 79.
    Suto F, Cahill SA, Greenwald I, Gross GJ. Early onset of QT interval prolongation and IKr downregulation in rabbits with compensated complete heart block. J Am Coll Cardiol 2001;37:91A (abstract)Google Scholar
  80. 80.
    Kleiman RB, Houser SR. Outward currents in normal and hypertrophied feline ventricular myocytes. Am J Physiol 1989;256:H1450–61PubMedGoogle Scholar
  81. 81.
    Furukawa T, Myerburg RJ, Furukawa N, Kimura S, Bassett AL. Metabolic inhibition of ICa,L and IK differs in feline left ventricular hypertrophy. Am J Physiol 1994;266:H1121–31PubMedGoogle Scholar
  82. 82.
    Lodge NJ, Normandin DE. Alterations in Itol, IKr and Ikl density in the BIO TO-2 strain of syrian myopathic hamsters. J Mol Cell Cardiol 1997;29:3211–21CrossRefPubMedGoogle Scholar
  83. 83.
    Volk T, Nguyen TH, Schultz JH, Faulhaber J, HE H. Regional alterations of repolarizing K+ currents among the left ventricular free wall of rats with ascending aortic stenosis. J Physiol 2001;530:443–55CrossRefPubMedGoogle Scholar
  84. 84.
    Ahmmed GU, Dong PH, Song G, Ball NA, Xu Y, Walsh RA, Chiamvimonvat N. Changes in Ca(2+) cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure. Circ Res 2000;86:558–70CrossRefPubMedGoogle Scholar
  85. 85.
    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 2001;88:476–482CrossRefPubMedGoogle Scholar
  86. 86.
    The Sicilian gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. Circulation 1991;84:1831–51CrossRefGoogle Scholar
  87. 87.
    Hondeghem LM, Snyders DJ. Class Ill antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. Circulation 1990;81:686–90CrossRefPubMedGoogle Scholar
  88. 88.
    van Opstal JM, Schoenmakers M, Verduyn SC, de Groot SHM, Leunissen HDM, Van der Hulst FF, Molenschot MMC, Wellens HJJ, Vos MA. Chronic amiodarone evokes no torsade de pointes arrhythmias despite QT lengthening in an animal model of acquired long QT syndrome. Circulation. In the press.Google Scholar
  89. 89.
    Hoppe UC, Marban E, Johns DC. Molecular dissection of cardiac repolarization by in vivo Kv4.3 gene transfer. J Clin Invest 2000;105:1077–84CrossRefPubMedGoogle Scholar
  90. 90.
    Hoppe UC, Marban E, Johns DC. Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1. Proc Natl Acad Sci U S A 2001;98:5335–40CrossRefPubMedGoogle Scholar
  91. 91.
    Donahue JK, Heldman AW, Fraser H, McDonald AD, Miller JM, Rade JJ, Eschenhagen T, Marban E. Focal modification of electrical conduction in the heart by viral gene transfer. Nat Med 2000;6:1395–8CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • M. Stengl
  • P. G. A. Volders
  • M. A. Vos

There are no affiliations available

Personalised recommendations