The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Modeling of Arrhythmogenic Automaticity Induced by Stretch in Rat Atrial Myocytes

  • Youm, Jae-Boum (National Research Laboratory for Mitochondrial Signaling, Department of Physiology and Biophysics, College of Medicine, Inje University) ;
  • Leem, Chae-Hun (Department of Physiology and the Institute for Calcium Research, University of Ulsan College of Medicine) ;
  • Zhang, Yin Hua (Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital) ;
  • Kim, Na-Ri (National Research Laboratory for Mitochondrial Signaling, Department of Physiology and Biophysics, College of Medicine, Inje University) ;
  • Han, Jin (National Research Laboratory for Mitochondrial Signaling, Department of Physiology and Biophysics, College of Medicine, Inje University) ;
  • Earm, Yung-E. (Department of Physiology and National Research Laboratory for Cellular Signalling, Seoul National University College of Medicine)
  • Published : 2008.10.31
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Abstract

Since first discovered in chick skeletal muscles, stretch-activated channels (SACs) have been proposed as a probable mechano-transducer of the mechanical stimulus at the cellular level. Channel properties have been studied in both the single-channel and the whole-cell level. There is growing evidence to indicate that major stretch-induced changes in electrical activity are mediated by activation of these channels. We aimed to investigate the mechanism of stretch-induced automaticity by exploiting a recent mathematical model of rat atrial myocytes which had been established to reproduce cellular activities such as the action potential, $Ca^{2+}$ transients, and contractile force. The incorporation of SACs into the mathematical model, based on experimental results, successfully reproduced the repetitive firing of spontaneous action potentials by stretch. The induced automaticity was composed of two phases. The early phase was driven by increased background conductance of voltage-gated $Na^+$ channel, whereas the later phase was driven by the reverse-mode operation of $Na^+/Ca^{2+}$ exchange current secondary to the accumulation of $Na^+$ and $Ca^{2+}$ through SACs. These results of simulation successfully demonstrate how the SACs can induce automaticity in a single atrial myocyte which may act as a focus to initiate and maintain atrial fibrillation in concert with other arrhythmogenic changes in the heart.

Keywords

References

  1. Baruscotti M, DiFrancesco D, Robinson RB. $Na^+$ current contribution to the diastolic depolarization in newborn rabbit SA node cells. Am J Physiol 279: H2303-H2309, 2000
  2. Baumgarten CM, Clemo HF. Swelling-activated chloride channels in cardiac physiology and pathophysiology. Prog Biophys Mol Biol 82: 25-42, 2003 https://doi.org/10.1016/S0079-6107(03)00003-8
  3. Bode F, Katchman A, Woosley RL, Franz MR. Gadolinium decreases stretch-induced vulnerability to atrial fibrillation. Circulation 101: 2200-2205, 2000 https://doi.org/10.1161/01.CIR.101.18.2200
  4. Bode F, Sachs F, Franz MR. Tarantula peptide inhibits atrial fibrillation. Nature 409: 35-36, 2001 https://doi.org/10.1038/35051165
  5. Boland J, Troquet J. Intracellular action potential changes induced in both ventricles of the rat by an acute right ventricular pressure overload. Cardiovasc Res 14: 735-740, 1980 https://doi.org/10.1093/cvr/14.12.735
  6. Boyle WA, Nerbonne JM. Two functionally distinct 4-aminopyridine-sensitive outward $K^+$ currents in rat atrial myocytes. J Gen Physiol 100: 1041-1067, 1992 https://doi.org/10.1085/jgp.100.6.1041
  7. Bustamante JO, Ruknudin A, Sachs F. Stretch-activated channels in heart cells: relevance to cardiac hypertrophy. J Cardiovasc Pharmacol 17: S110-S113, 1991 https://doi.org/10.1097/00005344-199117002-00024
  8. Craelius W. Stretch-activation of rat cardiac myocytes. Exp Physiol 78: 411-423, 1993 https://doi.org/10.1113/expphysiol.1993.sp003695
  9. Dean JW, Lab MJ. Arrhythmia in heart failure: role of mechanically induced changes in electrophysiology. Lancet 1: 1309-1312, 1989
  10. Ferrier GR. Digitalis arrhythmias: role of oscillatory afterpotentials. Prog Cardiovasc Dis 19: 459-474, 1977 https://doi.org/10.1016/0033-0620(77)90010-X
  11. Franz MR, Bode F. Mechano-electrical feedback underlying arrhythmias: the atrial fibrillation case. Prog Biophys Mol Biol 82: 163-174, 2003 https://doi.org/10.1016/S0079-6107(03)00013-0
  12. Franz MR, Burkhoff D, Yue DT, Sagawa K. Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts. Cardiovasc Res 23: 213-223, 1989 https://doi.org/10.1093/cvr/23.3.213
  13. Franz MR, Cima R, Wang D, Profitt D, Kurz R. Electrophysiological effects of myocardial stretch and mechanical determinants of stretch-activated arrhythmias [published erratum appears in Circulation 1992;86:1663]. Circulation 86: 968-978, 1992 https://doi.org/10.1161/01.CIR.86.3.968
  14. Hansen DE. Mechanoelectrical feedback effects of altering preload, afterload, and ventricular shortening. Am J Physiol 264: H423-H432, 1993
  15. Hordof AJ, Spotnitz A, Mary-Rabine L, Edie RN, Rosen MR. The cellular electrophysiologic effects of digitalis on human atrial fibers. Circulation 57: 223-229, 1978 https://doi.org/10.1161/01.CIR.57.2.223
  16. Hove-Madsen L, Llach A, Bayes-Genís A, Roura S, Rodriguez Font E, Arís A, Cinca J. Atrial fibrillation is associated with increased spontaneous calcium release from the sarcoplasmic reticulum in human atrial myocytes. Circulation 110: 1358-1363, 2004 https://doi.org/10.1161/01.CIR.0000141296.59876.87
  17. Hoyer J, Distler A, Haase W, Gögelein H, $Ca^{2+}$ influx through stretch-activated cation channels activates maxi $K^+$ channels in porcine endocardial endothelium. Proc Natl Acad Sci USA 91: 2367-2371
  18. Hu H, Sachs F. Mechanically activated currents in chick heart cells. J Membr Biol 154: 205-216, 1996 https://doi.org/10.1007/s002329900145
  19. Isenberg G, Kazanski V, Kondratev D, Gallitelli MF, Kiseleva I, Kamkin A. Differential effects of stretch and compression on membrane currents and [$Na^+$]c in ventricular myocytes. Prog Biophys Mol Biol 82: 43-56, 2003 https://doi.org/10.1016/S0079-6107(03)00004-X
  20. Kaufmann R, Theophile U. Automatiefördernde Dehnungseffekte an Purkinje-Fäden, Papillarmuskeln und Vorhoftrabekeln von Rhesus-Affen. Pflügers Arch 297: 174-189, 1967 https://doi.org/10.1007/BF00362710
  21. Kiseleva I, Kamkin A, Wagner KD, Theres H, Ladhoff A, Scholz H, Günther J, Lab MJ. Mechanoelectric feedback after left ventricular infarction in rats. Cardiovasc Res 45: 370-378, 2000 https://doi.org/10.1016/S0008-6363(99)00361-2
  22. Lab MJ. Mechanically dependent changes in action potentials recorded from the intact frog ventricle. Circ Res 42: 519-528, 1978 https://doi.org/10.1161/01.RES.42.4.519
  23. Lei M, Jones SA, Liu J, Lancaster MK, Fung SS, Dobrzynski H, Camelliti P, Maier SK, Noble D, Boyett MR. Requirement of neuronal- and cardiac-type sodium channels for murine sinoatrial node pacemaking. J Physiol 559: 835-848, 2004 https://doi.org/10.1113/jphysiol.2004.068643
  24. Maier SK, Westenbroek RE, Yamanushi TT, Dobrzynski H, Boyett MR, Catterall WA, Scheuer T. An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node. Proc Natl Acad Sci USA 100: 3507-3512, 2003
  25. Maltsev VA, Lakatta EG. Dynamic interactions of an intracellular $Ca^{2+}$ clock and membrane ion channel clock underlie robust initiation and regulation of cardiac pacemaker function. Cardiovasc Res 77: 274-284, 2008
  26. Mary-Rabine L, Albert A, Pham TD, Hordof A, Fenoglio JJ Jr, Malm JR, Rosen MR. The relationship of human atrial cellular electrophysiology to clinical function and ultrastructure. Circ Res 52: 188-199, 1983 https://doi.org/10.1161/01.RES.52.2.188
  27. Matsuoka S, Sarai N, Kuratomi S, Ono K, Noma A. Role of individual ionic current systems in ventricular cells hypothesized by a model study. Jpn J Physiol 53: 105-123, 2003 https://doi.org/10.2170/jjphysiol.53.105
  28. Niu W, Sachs F. Dynamic properties of stretch-activated $K^+$ channels in adult rat atrial myocytes. Prog Biophys Mol Biol 82: 121-135, 2003 https://doi.org/10.1016/S0079-6107(03)00010-5
  29. Noble D. Simulation of Na/Ca exchange activity during ischemia. Ann N Y Acad Sci 976: 431-437, 2002 https://doi.org/10.1111/j.1749-6632.2002.tb04772.x
  30. Noble D, Noble PJ. Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium-calcium overload. Heart 92: iv1-iv5, 2006
  31. Nuss HB, Balser JR, Orias DW, Lawrence JH, Tomaselli GF, Marban E. Coupling between fast and slow inactivation revealed by analysis of a point mutation (F1304Q) in $\mu$l rat skeletal muscle sodium channels. J Physiol 494: 411-429, 1996 https://doi.org/10.1113/jphysiol.1996.sp021502
  32. Prakash P, Meera P, Tripathi O. Effects of calcium channel blockers on spontaneous electrical activity of freshly isolated three-day-old embryonic chick ventricle. Reprod Fertil Dev 8: 921-929, 1996 https://doi.org/10.1071/RD9960921
  33. Psaty BM, Manolio TA, Kuller LH, Kronmal RA, Cushman M, Fried LP, White R, Furberg CD, Rautaharju PM. Incidence of and risk factors for atrial fibrillation in older adults. Circulation 96: 2455-2461, 1997 https://doi.org/10.1161/01.CIR.96.7.2455
  34. Rota M, Vassalle M. Patch-clamp analysis in canine cardiac Purkinje cells of a novel sodium component in the pacemaker range. J Physiol 548: 147-165, 2003 https://doi.org/10.1113/jphysiol.2003.039263
  35. Sadoshima J, Izumo S. Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: potential involvement of an autocrine/paracrine mechanism. EMBO J 12: 1681-1692, 1993
  36. Sanders L, Rakovic S, Lowe M, Mattick PA, Terrar DA. Fundamental importance of $Na^+$-$Ca^{2+}$ exchange for the pacemaking mechanism in guinea-pig sino-atrial node. J Physiol 571: 639-649, 2006 https://doi.org/10.1113/jphysiol.2005.100305
  37. Sarai N, Matsuoka S, Kuratomi S, Ono K, Noma A. Role of individual ionic current systems in the SA node hypothesized by a model study. Jpn J Physiol 53: 125-134, 2003 https://doi.org/10.2170/jjphysiol.53.125
  38. Satoh H, Mukai M, Urushida T, Katoh H, Terada H, Hayashi H. Importance of $Ca^{2+}$ influx by $Na^+$/$Ca^{2+}$ exchange under normal and sodium-loaded conditions in mammalian ventricles. Mol Cell Biochem 242: 11-17, 2003 https://doi.org/10.1023/A:1021192318882
  39. Sorota S. Swelling-induced chloride-sensitive current in canine atrial cells revealed by whole-cell patch-clamp method. Circ Res 70: 679-687, 1992 https://doi.org/10.1161/01.RES.70.4.679
  40. Taggart P. Mechano-electric feedback in the human heart. Cardiovasc Res 32: 38-43, 1996
  41. Terrenoire C, Lauritzen I, Lesage F, Romey G, Lazdunski M. A TREK-1-like potassium channel in atrial cells inhibited by beta-adrenergic stimulation and activated by volatile anesthetics. Circ Res 89: 336-342, 2001 https://doi.org/10.1161/hh1601.094979
  42. Tseng GN. Cell swelling increases membrane conductance of canine cardiac cells: evidence for a volume-sensitive Cl channel. Am J Physiol 262: C1056-C1068, 1992 https://doi.org/10.1152/ajpcell.1992.262.4.C1056
  43. Vandenburgh HH. Mechanical forces and their second messengers in stimulating cell growth in vitro. Am J Physiol 262: R350-R355, 1992
  44. Vassalle M, Scidá EE. The role of sodium in spontaneous discharge in the absence and in the presence of strophanthidin. Fed Proc 38: 880, 1979
  45. Vaziri SM, Larson MG, Benjamin EJ, Levy D. Echocardiographic predictors of nonrheumatic atrial fibrillation. The Framingham Heart Study. Circulation 89: 724-730, 1994 https://doi.org/10.1161/01.CIR.89.2.724
  46. Vinogradova TM, Maltsev VA, Bogdanov KY, Lyashkov AE, Lakatta EG. Rhythmic $Ca^{2+}$ oscillations drive sinoatrial nodal cell pacemaker function to make the heart tick. Ann N Y Acad Sci 1047: 138-156, 2005 https://doi.org/10.1196/annals.1341.013
  47. Wagner MB, Kumar R, Joyner RW, Wang Y. Induced automaticity in isolated rat atrial cells by incorporation of a stretch-activated conductance. Pflugers Arch 447: 819-829, 2004 https://doi.org/10.1007/s00424-003-1208-7
  48. Youm JB. Stretch-activated $k^+$ channels in rat atrial myocytes. Korean J Physiol Pharmacol 7: 341-348, 2003
  49. Youm JB, Han J, Kim N, Zhang YH, Kim E, Joo H, Leem CH, Kim SJ, Cha KA, Earm YE. Role of stretch-activated channels on the stretch-induced changes of rat atrial myocytes. Prog Biophys Mol Biol 90: 186-206, 2006 https://doi.org/10.1016/j.pbiomolbio.2005.06.003
  50. Zhang YH, Youm JB, Sung HK, Lee SH, Ryu SY, Ho WK, Earm YE. Stretch-activated and background non-selective cation channels in rat atrial myocytes. J Physiol 523: 607-619, 2000 https://doi.org/10.1111/j.1469-7793.2000.00607.x