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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 May;118(2):407–413. doi: 10.1111/j.1476-5381.1996.tb15417.x

Effect of gadolinium on stretch-induced changes in contraction and intracellularly recorded action- and afterpotentials of rat isolated atrium.

P Tavi 1, M Laine 1, M Weckström 1
PMCID: PMC1909639  PMID: 8735645

Abstract

1. Atrial arrhythmias, like atrial fibrillation and extrasystoles, are common in clinical situations when atrial pressure is increased. Although cardiac mechanoelectrical feedback has been under intensive study for many years, the mechanisms of stretch-induced arrhythmias are not known in detail. This is partly due to methodological difficulties in recording intracellular voltage during stretch stimulation. In this study we investigated the effects of gadolinium (Gd3+), a blocker of stretch-activated (SA) channels, on stretch-induced changes in rat atrial action potentials and contraction force. 2. By intracellular voltage recordings from rat isolated atria we studied the effects of Gd3+ (80 microM) on stretch-induced changes in action potentials. The stretch was induced by increasing pressure inside the atrium (1 mmHg to 7 mmHg). An elastic electrode holder that moved along the atrial tissue was used in the recordings. Thus the mechanical artifacts were eliminated and the cell-electrode contact was made more stable. To examine the influence of Gd3+ on atrial contraction we stretched the atria at different diastolic pressure levels (1 to 7 mmHg) with Gd3+ application of (80 microM) or diltiazem (5.0 microM). Contraction force was monitored by recording the pressure changes generated by the atrial contractions. 3. Our results show that: (1) atrial stretch induces delayed afterdepolarizations (DADs), increase in action potential amplitude and increase in relative conduction speed; (ii) Gd3+ blocks stretch-induced DADs and action potential changes; (iii) Gd3+ inhibits pressure-stimulated increase in the atrial contraction force, while similar inhibition is not observed with diltiazem, a blocker of L-type calcium channels. 4. This study suggests that Gd3+ inhibits stretch-induced changes in cell electrophysiology and contraction in the rat atrial cells and that the effects of gadolinium are due to rather specific block of stretch-activated ion channels with only a small effect on voltage-activated calcium channels.

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Selected References

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  1. Allen D. G., Kurihara S. The effects of muscle length on intracellular calcium transients in mammalian cardiac muscle. J Physiol. 1982 Jun;327:79–94. doi: 10.1113/jphysiol.1982.sp014221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen D. G., Nichols C. G., Smith G. L. The effects of changes in muscle length during diastole on the calcium transient in ferret ventricular muscle. J Physiol. 1988 Dec;406:359–370. doi: 10.1113/jphysiol.1988.sp017385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arlock P., Katzung B. G. Effects of sodium substitutes on transient inward current and tension in guinea-pig and ferret papillary muscle. J Physiol. 1985 Mar;360:105–120. doi: 10.1113/jphysiol.1985.sp015606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boland L. M., Brown T. A., Dingledine R. Gadolinium block of calcium channels: influence of bicarbonate. Brain Res. 1991 Nov 1;563(1-2):142–150. doi: 10.1016/0006-8993(91)91527-8. [DOI] [PubMed] [Google Scholar]
  5. Boyle W. A., Nerbonne J. M. A novel type of depolarization-activated K+ current in isolated adult rat atrial myocytes. Am J Physiol. 1991 Apr;260(4 Pt 2):H1236–H1247. doi: 10.1152/ajpheart.1991.260.4.H1236. [DOI] [PubMed] [Google Scholar]
  6. Bustamante J. O., Ruknudin A., Sachs F. Stretch-activated channels in heart cells: relevance to cardiac hypertrophy. J Cardiovasc Pharmacol. 1991;17 (Suppl 2):S110–S113. doi: 10.1097/00005344-199117002-00024. [DOI] [PubMed] [Google Scholar]
  7. Dominguez G., Fozzard H. A. Effect of stretch on conduction velocity and cable properties of cardiac Purkinje fibers. Am J Physiol. 1979 Sep;237(3):C119–C124. doi: 10.1152/ajpcell.1979.237.3.C119. [DOI] [PubMed] [Google Scholar]
  8. Ebner F., Korth M., Kühlkamp V. The reaction of ouabain with the sodium pump of guinea-pig myocardium in relation to its inotropic effect. J Physiol. 1986 Oct;379:187–203. doi: 10.1113/jphysiol.1986.sp016247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Franz M. R., Burkhoff D., Yue D. T., Sagawa K. Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts. Cardiovasc Res. 1989 Mar;23(3):213–223. doi: 10.1093/cvr/23.3.213. [DOI] [PubMed] [Google Scholar]
  10. Franz M. R., Cima R., Wang D., Profitt D., Kurz R. Electrophysiological effects of myocardial stretch and mechanical determinants of stretch-activated arrhythmias. Circulation. 1992 Sep;86(3):968–978. doi: 10.1161/01.cir.86.3.968. [DOI] [PubMed] [Google Scholar]
  11. Gannier F., White E., Lacampagne A., Garnier D., Le Guennec J. Y. Streptomycin reverses a large stretch induced increases in [Ca2+]i in isolated guinea pig ventricular myocytes. Cardiovasc Res. 1994 Aug;28(8):1193–1198. doi: 10.1093/cvr/28.8.1193. [DOI] [PubMed] [Google Scholar]
  12. Guharay F., Sachs F. Stretch-activated single ion channel currents in tissue-cultured embryonic chick skeletal muscle. J Physiol. 1984 Jul;352:685–701. doi: 10.1113/jphysiol.1984.sp015317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hansen D. E., Borganelli M., Stacy G. P., Jr, Taylor L. K. Dose-dependent inhibition of stretch-induced arrhythmias by gadolinium in isolated canine ventricles. Evidence for a unique mode of antiarrhythmic action. Circ Res. 1991 Sep;69(3):820–831. doi: 10.1161/01.res.69.3.820. [DOI] [PubMed] [Google Scholar]
  14. Hansen D. E., Craig C. S., Hondeghem L. M. Stretch-induced arrhythmias in the isolated canine ventricle. Evidence for the importance of mechanoelectrical feedback. Circulation. 1990 Mar;81(3):1094–1105. doi: 10.1161/01.cir.81.3.1094. [DOI] [PubMed] [Google Scholar]
  15. January C. T., Fozzard H. A. Delayed afterdepolarizations in heart muscle: mechanisms and relevance. Pharmacol Rev. 1988 Sep;40(3):219–227. [PubMed] [Google Scholar]
  16. Kass R. S., Lederer W. J., Tsien R. W., Weingart R. Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978 Aug;281:187–208. doi: 10.1113/jphysiol.1978.sp012416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kass R. S., Tsien R. W., Weingart R. Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978 Aug;281:209–226. doi: 10.1113/jphysiol.1978.sp012417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kim D. A mechanosensitive K+ channel in heart cells. Activation by arachidonic acid. J Gen Physiol. 1992 Dec;100(6):1021–1040. doi: 10.1085/jgp.100.6.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kim D. Novel cation-selective mechanosensitive ion channel in the atrial cell membrane. Circ Res. 1993 Jan;72(1):225–231. doi: 10.1161/01.res.72.1.225. [DOI] [PubMed] [Google Scholar]
  20. Komuro I., Katoh Y., Kaida T., Shibazaki Y., Kurabayashi M., Hoh E., Takaku F., Yazaki Y. Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. Possible role of protein kinase C activation. J Biol Chem. 1991 Jan 15;266(2):1265–1268. [PubMed] [Google Scholar]
  21. Lab M. J. Mechanically dependent changes in action potentials recorded from the intact frog ventricle. Circ Res. 1978 Apr;42(4):519–528. doi: 10.1161/01.res.42.4.519. [DOI] [PubMed] [Google Scholar]
  22. Lab M. J. Transient depolarisation and action potential alterations following mechanical changes in isolated myocardium. Cardiovasc Res. 1980 Dec;14(11):624–637. doi: 10.1093/cvr/14.11.624. [DOI] [PubMed] [Google Scholar]
  23. Lab M. J., Zhou B. Y., Spencer C. I., Horner S. M., Seed W. A. Effects of gadolinium on length-dependent force in guinea-pig papillary muscle. Exp Physiol. 1994 Mar;79(2):249–255. doi: 10.1113/expphysiol.1994.sp003758. [DOI] [PubMed] [Google Scholar]
  24. Lacampagne A., Gannier F., Argibay J., Garnier D., Le Guennec J. Y. The stretch-activated ion channel blocker gadolinium also blocks L-type calcium channels in isolated ventricular myocytes of the guinea-pig. Biochim Biophys Acta. 1994 Apr 20;1191(1):205–208. doi: 10.1016/0005-2736(94)90250-x. [DOI] [PubMed] [Google Scholar]
  25. Laine M., Arjamaa O., Vuolteenaho O., Ruskoaho H., Weckström M. Block of stretch-activated atrial natriuretic peptide secretion by gadolinium in isolated rat atrium. J Physiol. 1994 Nov 1;480(Pt 3):553–561. doi: 10.1113/jphysiol.1994.sp020383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Laine M., Weckström M., Vuolteenaho O., Arjamaa O. Effect of ryanodine on atrial natriuretic peptide secretion by contracting and quiescent rat atrium. Pflugers Arch. 1994 Feb;426(3-4):276–283. doi: 10.1007/BF00374782. [DOI] [PubMed] [Google Scholar]
  27. Lansman J. B. Blockade of current through single calcium channels by trivalent lanthanide cations. Effect of ionic radius on the rates of ion entry and exit. J Gen Physiol. 1990 Apr;95(4):679–696. doi: 10.1085/jgp.95.4.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Le Guennec J. Y., White E., Gannier F., Argibay J. A., Garnier D. Stretch-induced increase of resting intracellular calcium concentration in single guinea-pig ventricular myocytes. Exp Physiol. 1991 Nov;76(6):975–978. doi: 10.1113/expphysiol.1991.sp003560. [DOI] [PubMed] [Google Scholar]
  29. McBride D. W., Jr, Hamill O. P. Pressure-clamp technique for measurement of the relaxation kinetics of mechanosensitive channels. Trends Neurosci. 1993 Sep;16(9):341–345. doi: 10.1016/0166-2236(93)90089-5. [DOI] [PubMed] [Google Scholar]
  30. Morris C. E. Mechanosensitive ion channels. J Membr Biol. 1990 Feb;113(2):93–107. doi: 10.1007/BF01872883. [DOI] [PubMed] [Google Scholar]
  31. Nakagawa A., Arita M., Shimada T., Shirabe J. Effects of mechanical stretch on the membrane potential of guinea pig ventricular muscles. Jpn J Physiol. 1988;38(6):819–838. doi: 10.2170/jjphysiol.38.819. [DOI] [PubMed] [Google Scholar]
  32. Ravelli F., Disertori M., Cozzi F., Antolini R., Allessie M. A. Ventricular beats induce variations in cycle length of rapid (type II) atrial flutter in humans. Evidence of leading circle reentry. Circulation. 1994 May;89(5):2107–2116. doi: 10.1161/01.cir.89.5.2107. [DOI] [PubMed] [Google Scholar]
  33. Ruknudin A., Sachs F., Bustamante J. O. Stretch-activated ion channels in tissue-cultured chick heart. Am J Physiol. 1993 Mar;264(3 Pt 2):H960–H972. doi: 10.1152/ajpheart.1993.264.3.H960. [DOI] [PubMed] [Google Scholar]
  34. Sachs F. Mechanical transduction in biological systems. Crit Rev Biomed Eng. 1988;16(2):141–169. [PubMed] [Google Scholar]
  35. Sadoshima J., Takahashi T., Jahn L., Izumo S. Roles of mechano-sensitive ion channels, cytoskeleton, and contractile activity in stretch-induced immediate-early gene expression and hypertrophy of cardiac myocytes. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9905–9909. doi: 10.1073/pnas.89.20.9905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sigurdson W., Ruknudin A., Sachs F. Calcium imaging of mechanically induced fluxes in tissue-cultured chick heart: role of stretch-activated ion channels. Am J Physiol. 1992 Apr;262(4 Pt 2):H1110–H1115. doi: 10.1152/ajpheart.1992.262.4.H1110. [DOI] [PubMed] [Google Scholar]
  37. Stacy G. P., Jr, Jobe R. L., Taylor L. K., Hansen D. E. Stretch-induced depolarizations as a trigger of arrhythmias in isolated canine left ventricles. Am J Physiol. 1992 Aug;263(2 Pt 2):H613–H621. doi: 10.1152/ajpheart.1992.263.2.H613. [DOI] [PubMed] [Google Scholar]
  38. Stevenson K. M., Lumbers E. R. Effects of angiotensin II in fetal sheep and modification of its actions by indomethacin. J Physiol. 1995 Aug 15;487(1):147–158. doi: 10.1113/jphysiol.1995.sp020867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Van Wagoner D. R. Mechanosensitive gating of atrial ATP-sensitive potassium channels. Circ Res. 1993 May;72(5):973–983. doi: 10.1161/01.res.72.5.973. [DOI] [PubMed] [Google Scholar]
  40. Varró A., Lathrop D. A., Hester S. B., Nánási P. P., Papp J. G. Ionic currents and action potentials in rabbit, rat, and guinea pig ventricular myocytes. Basic Res Cardiol. 1993 Mar-Apr;88(2):93–102. doi: 10.1007/BF00798257. [DOI] [PubMed] [Google Scholar]
  41. White E., Le Guennec J. Y., Nigretto J. M., Gannier F., Argibay J. A., Garnier D. The effects of increasing cell length on auxotonic contractions; membrane potential and intracellular calcium transients in single guinea-pig ventricular myocytes. Exp Physiol. 1993 Jan;78(1):65–78. doi: 10.1113/expphysiol.1993.sp003671. [DOI] [PubMed] [Google Scholar]
  42. Yang X. C., Sachs F. Block of stretch-activated ion channels in Xenopus oocytes by gadolinium and calcium ions. Science. 1989 Feb 24;243(4894 Pt 1):1068–1071. doi: 10.1126/science.2466333. [DOI] [PubMed] [Google Scholar]

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