Journal of Biomedical Science

, Volume 1, Issue 3, pp 193–200 | Cite as

Adrenergic modulation of potassium currents in isolated human atrial myocytes

  • Ming-Jai Su
  • Jo-Feng Chi
  • Shu-Hsun Chu
Original Paper


The adrenergic modulation of inwardly rectifying and depolarization-activated outward potassium currents was studied in single cardiac myocytes obtained from the human atrium. Membrane currents were recorded in enzymatically dissociated cells using the whole-cell voltage-clamp technique. It was observed that, in the presence or absence of atenolol (or 1 µM propranolol), 30 µM phenylephrine attenuated inwardly rectifying and depolarization-activated outward potassium currents including both transient and late-activated current. This suppressant effect of phenylephrine could be prevented by pretreatment with an α-adrenoceptor antagonist. Isoproterenol (30 µM) increased the late outward potassium current and net transient outward current. It is concluded that, in human atrial myocytes, α-adrenergic activation reduces depolarization-activated transient and late outward potassium current and inwardly rectifying background potassium current. β-Adrenergic activation resulted in an increase in the depolarization-activated transient and late outward potassium current.

Key Words

Human atrial myocytes Potassium currents Adrenergic modulation Phenylephrine Isoproterenol 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aass H, Skomedal T, Osnes JB, Fjeld NB, Klingen G, Langslet A, Svennevig J, Semb G. Noradrenaline evokes an α-adrenoceptor-mediated inotropic effect in human ventricular myocardium. Acta Pharmacol Toxicol 58:88–90;1986.Google Scholar
  2. 2.
    Apkon M, Nerbonne JM. α1-Adrenergic agonists selectively suppress voltage-dependent K+ currents in rat ventricular myocytes. Proc Natl Acad Sci USA 85:8756–8760;1988.Google Scholar
  3. 3.
    Bohm M, Diet F, Feiler G, Kemkes B, Erdmann E. α-Adrenoceptors and α-adrenergic-mediated positive inotropic effects in failing human myocardium. J Cardiovasc Pharmacol 12:357–364;1988.Google Scholar
  4. 4.
    Braun AP, Fedida D, Giles WR. Activation of α1-adrenoceptors modulates the inwardly rectifying potassium currents of mammalian atrial myocytes. Pflügers Arch 421:431–439;1992.Google Scholar
  5. 5.
    Bristow MR, Ginsburg R, Minobe WA, Cubicciotti RS, Sageman WS, Lurie K, Billingham ME, Harrison DC. Decreased catecholamines sensitivity and β-adrenergic receptor density in failing human hearts. N Engl J Med 305:205–211;1982.Google Scholar
  6. 6.
    Bristow MR, Hershberger RE, Port JD, Gilbert EM, Sandoval A, Rasmussen R, Cates AE, Feldman AM. β-Adrenergic pathways in nonfailing and failing human ventricular myocardium. Circulation 82(suppl 1):12–25;1990.Google Scholar
  7. 7.
    Bristow MR, Kantrowitz NE, Ginsburg R, Fowler MB. β-Adrenergic function in heart muscle disease and heart failure. J Mol Cell Cardiol 17(suppl 2):41–52;1985.Google Scholar
  8. 8.
    Bristow MR, Minobe W, Rasmussen R, Hershberger RE, Hoffman BB. α1-Adrenergic receptors in nonfailing and failing human heart. J Pharmacol Exp Ther 247:1039–1045;1988.Google Scholar
  9. 9.
    Brodde OE. β1-Adrenoceptors in the human heart: Properties, function, and alterations in chronic heart failure. Pharmacol Rev 43:203–242;1991.Google Scholar
  10. 10.
    Brown HF, Noble SJ. Effects of adrenaline on membrane currents underlying pacemaker activity in frog atrial muscle. J Physiol (Lond) 238:51–53;1974.Google Scholar
  11. 11.
    Brückner R, Meyer W, Mügge A, Schmitz W, Scholz H. α-Adrenoceptor-mediated positive inotropic effect of phenylephrine in isolated human ventricular myocardium. Eur J Pharmacol 99:345–347;1984.Google Scholar
  12. 12.
    Duchatelle-Gourdon I, Hartzell HC, Lagrutta AA. Modulation of the delayed rectifier potassium current in frog cardiomyocytes by beta-adrenergic agonists and magnesium. J Physiol (Lond) 415:251–274;1989.Google Scholar
  13. 13.
    Escande D, Coulombe A, Faivre JF, Deroubaix E, Coraboeuf E. Two types of transient outward current in adult human atrial cells. Am J Physiol 252:H142-H148;1987.Google Scholar
  14. 14.
    Fedida D, Braun AP, Giles WR. α1-Adrenoceptors reduce background K+ current in rabbit ventricular myocytes. J Physiol (Lond) 441:673–684;1991.Google Scholar
  15. 15.
    Fedida D, Shimoni Y, Giles WR. A novel effect of norepinephrine on cardiac cells is mediated by α1-adrenoceptors. Am J Physiol 256:H1500-H1504;1989.Google Scholar
  16. 16.
    Fedida D, Shimoni Y, Giles WR. Alpha-adrenergic modulation of the transient outward current in rabbit atrial myocytes. J Physiol (Lond) 423:257–277;1990.Google Scholar
  17. 17.
    Fedida D, Braun AP, Giles WR. Changes in the rectifying potassium currents of atrial myocytes induced by α1-adrenoceptors in the presence and absence of acetylcholine. Pflügers Arch 421:431–439;1992.Google Scholar
  18. 18.
    Fleming JW, Wisler PL, Watanabe AM. Signal transduction by G proteins in cardiac tissues. Circulation 85:420–433;1992.Google Scholar
  19. 19.
    Giles WR, Nakajima T, Ono K, Shibata EF. Modulation of the delayed rectifier K+ current by isoprenaline in bull-frog atrial myocytes. J Physiol (Lond) 415:233–249;1989.Google Scholar
  20. 20.
    Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high-resolution current recordings from cells and cell-free membrane patch. Eur J Pharmacol 341:85–100;1981.Google Scholar
  21. 21.
    Heidbüchel H, Vereecke J, Carmeliet E. Different K+ channels in human atrial cells. Pflügers Arch 414(suppl 1):171–172;1989.Google Scholar
  22. 22.
    Hescheler J, Nawrath H, Tang W, Trautwein W. Adrenoceptor-mediated changes of excitation and contraction in ventricular heart muscle from guinea pig and rabbits. J Physiol (Lond) 397:657–670;1988.Google Scholar
  23. 23.
    Horn EM, Johnson NJ, Bilezikian JP, Rosen MR. Developmental changes in the electrophysiological properties and the beta-adrenergic receptor-effector complex in atrial fibers of the canine coronary sinus. Circ Res 65:325–333;1989.Google Scholar
  24. 24.
    Jahnel U, Jakob H, Nawrath H. Electrophysiologic and inotropic effects of α-adrenoceptor stimulation in human isolated atrial heart muscle. Naunyn Schmiedebergs Arch Pharmacol 346:82–87;1992.Google Scholar
  25. 25.
    Jahnel U, Nawrath H, Carmeliet E, Vereecke J. Depolarization-induced influx of sodium in response to phenylephrine in rat atrial heart muscle. J Physiol (Lond) 432:621–637;1991.Google Scholar
  26. 26.
    Jones CR, Molenaar KP, Summers RJ. New views of human cardiac β-adrenoceptors. J Mol Cell Cardiol 21:519–535;1989.Google Scholar
  27. 27.
    Kass RS, Wiegers SE. The ionic basis of concentration-related effects of noradrenaline on the action potential of calf cardiac Purkinje fibers. J Physiol (Lond) 322:541–558;1982.Google Scholar
  28. 28.
    Kimura S, Bassett AL, Kohya T, Kozlovskis PL, Myerburg RJ. Automaticity, triggered activity, and responses to adrenergic stimulation in cat subendocardial Purkinje fibers after healing of myocardial infarction. Circulation 75:651–660;1987.Google Scholar
  29. 29.
    Kimura S, Cameron JS, Kozlovskis PL, Bassett AL, Myerburg RJ. Delayed afterdepolarizations and triggered activity induced in feline Purkinje fibers by α-adrenergic stimulation in the presence of elevated calcium levels. Circulation 70:1074–1082;1984.Google Scholar
  30. 30.
    Kurachi Y, Ito H, Sugimoto T, Shimizu T, Miki I, Ui M. α-Adrenergic activation of the muscarinic K+ channel is mediated by arachidonic acid metabolites. Pflügers Arch 414:102–104;1989.Google Scholar
  31. 31.
    Lungren E, Terracio L, Allen Do, Bory TK. Beta-receptor density and function are maintained by adult cardiac myocytes as they progress into culture. In: Clark WA, Decker RS, Bory TK, eds. Biology of Isolated Adult Cardiac Myocytes. New York, Elsevier, 253–256;1988.Google Scholar
  32. 32.
    Matsuura H, Ehara T, Imoto Y. An analysis of the delayed outward current in single ventricular cells of the guinea-pig. Pflügers Arch 410:596–603;1987.Google Scholar
  33. 33.
    Priori SG, Corr PB. Mechanisms underlying early and delayed afterdepolarizations induced by catecholamines. Am J Physiol 258:H1796-H1805;1990.Google Scholar
  34. 34.
    Ravens U, Wang XL, Wettwer E. Alpha adrenoceptor stimulation reduces outward currents in rat ventricular myocytes. J Pharmacol Exp Ther 250:364–370;1989.Google Scholar
  35. 35.
    Schmitz W, Scholz H, Erdmann E. Effects of α- and β-adrenergic agonists, phosphodiesterase inhibitors and adenosine on isolated human heart muscle preparations. Trends Pharmacol Sci 8:447–450;1987.Google Scholar
  36. 36.
    Schümann HJ, Wagner J, Knorr A, Reidemeister JC, Sadony V, Schramm G. Demonstration in human atrial preparations of α-adrenoceptors mediating positive inotropic effects. Naunyn Schmiedebergs Arch Pharmacol 302:333–336;1987.Google Scholar
  37. 37.
    Shah A, Cohen IS, Rosen MR. Stimulation of cardiac alpha receptors increases Na/K pump current and decreases GK via a pertussis toxin-sensitive pathway. Biophys J 54:219–225;1988.Google Scholar
  38. 38.
    Sheridan DJ, Penkoske PA, Sobel BE, Corr PR. α-Adrenergic contributions to dysrhythmia during myocardial ischaemia and reperfusion in cats. J Clin Invest 65:161–171;1980.Google Scholar
  39. 39.
    Shibata EF, Drury T, Refsum H, Aldrete V, Giles WR. Contributions of a transient outward current to repolarization in human atrium. Am J Physiol 257:H1773-H1781;1989.Google Scholar
  40. 40.
    Steinfath M, Chen YY, Lavicky J, Magnussen O, Nose M, Rosswag S, Schmitz W, Scholz H. Cardiac α1-adrenoceptor densities in different mammalian species. Br J Pharmacol 107:185–188;1992.Google Scholar
  41. 41.
    Steinfath M, Danielsen W, Leyen von der H, Mende U, Meyer W, Neumann J, Nose M, Reich T, Schmitz W, Scholz H, Starbatty J, Stein B, Doring V, Kalmar P, Haverich A. Reduced α1- and β2-adrenoceptor-mediated positive inotropic effects in human endstage heart failure. Br J Pharmacol 105:463–469;1992.Google Scholar
  42. 42.
    Tohse N, Nakaya H, Hattori Y, Endou M, Kanno M. Inhibitory effect mediated by α1-adrenoceptors on transient outward current in isolated rat ventricular cells. Pflügers Arch 415:575–581;1999.Google Scholar
  43. 43.
    Tsien RW, Giles WR, Greengard P. Cyclic AMP mediates the effect of adrenaline on cardiac Purkinje fibers. Nature 240:181–183;1972.Google Scholar
  44. 44.
    Wagner J, Brodde OE. On the presence and distribution of α-adrenoceptors in the heart of various mammalian species. Naunyn Schmiedebergs Arch Pharmacol 302:239–254;1978.Google Scholar
  45. 45.
    Walsh KB, Begenisich TB, Kass RS. β-Adrenergic modulation in the heart: Independent regulation of K and Ca channels. Pflügers Arch 411:232–234;1988.Google Scholar
  46. 46.
    Walsh KB, Begenisich TB, Kass RS. Beta-adrenergic modulation of cardiac ion channels: Differential temperature sensitivity of potassium and calcium current. J Gen Physiol 93:841–854;1989.Google Scholar
  47. 47.
    Wang Z, Fermini B, Nattel S. Delayed rectifier outward current and repolarization in human atrial myocytes. Circ Res 73:276–285;1993.Google Scholar

Copyright information

© National Science Council 1994

Authors and Affiliations

  • Ming-Jai Su
    • 2
  • Jo-Feng Chi
    • 2
  • Shu-Hsun Chu
    • 1
  1. 1.Department of Surgery, College of MedicineNational Taiwan UniversityTaipeiTaiwan, ROC
  2. 2.Pharmacological Institute College of MedicineNational Taiwan UniversityTaipeiTaiwan (ROC)

Personalised recommendations