AIMS Biophysics, 2014, 1(1): 16-30. doi: 10.3934/biophy.2014.1.16

Research article

Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

Mechanoelectric feedback does not contribute to the Frank-Starling relation in the rat and guinea pig heart

Discipline of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005 Australia

Mechanoelectric feedback (MEF) is the process by which mechanical forces on the myocardium can alter its electrical properties. The effect can be large enough to induce ectopic beats or fibrillation. However, the role of MEF at physiological levels of mechanical stress is not clear. We have investigated alteration in action potential morphology in rat and guinea pig ventricle and in rat atrial tissue at levels of stretch near the plateau of the Frank-Starling curve. Stretch of >100 mm.Hg End Diastolic Left Ventricular Pressure (EDLVP) or rapidly applied stretch (EDLVP increased by 25 mm.Hg within 100 ms) often triggered ectopic beats in isolated rat and guinea-pig hearts. However, ventricular epicardial monophasic action potentials (MAPs) recorded during stretch to EDLVP up to 30 mm. Hg showed no consistent changes in action potential duration (at APD20, APD50 or APD80) in either species. MAP recording detected APD prolongation with very small concentrations of 4-AP (10 μM), confirming the discrimination of the recording technique. In isolated rat atrial strips, no changes in intracellular action potential morphology or membrane potential were seen when stretched to levels producing an optimum increase in contractility. We conclude that alteration in action potential morphology with stretch does not contribute to the Frank-Starling relation in ventricle of rat or guinea-pig isolated heart, or in rat atrial tissue.
  Article Metrics


1. Allen DG, Kentish JC (1985) The cellular basis of the length-tension relation in cardiac muscle. J Mol Cell Cardiol 17: 821–840.

2. Babu A, Sonnenblick E, Gulati J (1988) Molecular basis for the influence of muscle length on myocardial performance. Science 240: 74–76.

3. Bainbridge FA (1915) The influence of venous filling upon the rate of the heart. J Physiol 50:65–84.

4. Blinks JR (1956) Positive chronotropic effect of increasing right atrial pressure in the isolated mammalian heart. Am J Physiol 186: 299–303.

5. Bockenhauer D, Zilberberg N, Goldstein SA (2001) KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Nat Neurosci 4: 486–491.

6. Bustamante JO, Ruknudin A, Sachs F (1991) Stretch-activated channels in heart cells: relevance to cardiac hypertrophy. J Cardiovasc Pharmacol 17 Suppl 2: S110–113.

7. Calaghan SC, Belus A, White E (2003) Do stretch-induced changes in intracellular calcium modify the electrical activity of cardiac muscle? Prog Biophys Mol Biol 82: 81–95.

8. Calaghan SC, Le Guennec JY, White E (2004) Cytoskeletal modulation of electrical and mechanical activity in cardiac myocytes. Prog Biophys Mol Biol 84: 29–59.

9. Calkins H, Levine JH, Kass DA (1991) Electrophysiological effect of varied rate and extent of acute in vivo left ventricular load increase. Cardiovasc Res 25: 637–644.

10. Dean JW, Lab MJ (1990) Regional changes in ventricular excitability during load manipulation of the in situ pig heart. J Physiol 429: 387–400.

11. Franz MR (1996) Mechano-electrical feedback in ventricular myocardium. Cardiovasc Res 32:15–4.

12. Franz MR, Cima R, Wang D, et al. (1992) Electrophysiological effects of myocardial stretch and mechanical determinants of stretch-activated arrhythmias. Circulation 86: 968–978.

13. Fuchs F, Martyn DA (2005) Length-dependent Ca(2+) activation in cardiac muscle: some remaining questions. J Muscle Res Cell Motil 26: 199–212.

14. Hansen DE, Craig CS, Hondeghem LM (1990) Stretch-induced arrhythmias in the isolated canine ventricle. Evidence for the importance of mechanoelectrical feedback. Circulation 81:1094–1105.

15. Hennekes R, Kaufmann R, Lab M (1981) The dependence of cardiac membrane excitation and contractile ability on active muscle shortening (cat papillary muscle). Pflugers Arch 392: 22–28.

16. Hu H, Sachs F (1997) Stretch-activated ion channels in the heart. J Mol Cell Cardiol 29:1511–1523.

17. Kamkin A, Kiseleva I, Wagner KD, et al. (2000) Mechano-electric feedback in right atrium after left ventricular infarction in rats. J Mol Cell Cardiol 32: 465–477.

18. Kaufmann RL, Lab MJ, Hennekes R, et al. (1971) Feedback interaction of mechanical and electrical events in the isolated mammalian ventricular myocardium (cat papillary muscle). Pflugers Arch 324: 100–123.

19. Kelly D, Mackenzie L, Hunter P, et al. (2006) Gene expression of stretch-activated channels and mechanoelectric feedback in the heart. Clin Exp Pharmacol Physiol 33: 642–648.

20. Kiseleva I, Kamkin A, Wagner KD, et al. (2000) Mechanoelectric feedback after left ventricular infarction in rats. Cardiovasc Res 45: 370–378.

21. Kohl P, Bollensdorff C, Garny A (2006) Effects of mechanosensitive ion channels on ventricular electrophysiology: experimental and theoretical models. Exp Physiol 91: 307–321.

22. Lab MJ (1999) Mechanosensitivity as an integrative system in heart: an audit. Prog Biophys Mol Biol 71: 7–27.

23. Lab MJ, Allen DG, Orchard CH (1984) The effects of shortening on myoplasmic calcium concentration and on the action potential in mammalian ventricular muscle. Circ Res 55:825–829.

24. Lange G, Lu HH, Chang A, et al. (1966) Effect of stretch on the isolated cat sinoatrial node. Am J Physiol 211: 1192–1196.

25. Legrice IJ, Hunter PJ, Smaill BH (1997) Laminar structure of the heart: a mathematical model. Am J Physiol 272: H2466–2476.

26.Nazir SA, Lab MJ (1996) Mechanoelectric feedback in the atrium of the isolated guinea-pig heart. Cardiovasc Res 32: 112–119.

27. Nickerson D, Niederer S, Stevens C, et al. (2006) A computational model of cardiac electromechanics. Conf Proc IEEE Eng Med Biol Soc 1: 5311–5314.

28. Ravens U (2003) Mechano-electric feedback and arrhythmias. Prog Biophys Mol Biol 82:255–266.

29. Reiter MJ, Synhorst DP, Mann DE (1988) Electrophysiological effects of acute ventricular dilatation in the isolated rabbit heart. Circ Res 62: 554–562.

30. Riemer TL, Tung L (2003) Stretch-induced excitation and action potential changes of single cardiac cells. Prog Biophys Mol Biol 82: 97–110.

31. Rozenberg S, Tavernier B, Riou B, et al. (2006) Severe impairment of ventricular compliance accounts for advanced age-associated hemodynamic dysfunction in rats. Exp Gerontol 41:289–295.

32. Sackin H (1995) Mechanosensitive channels. Annu Rev Physiol 57: 333–353.

33. Stacy GP, Jr, Jobe RL, Taylor LK, et al. (1992) Stretch-induced depolarizations as a trigger of arrhythmias in isolated canine left ventricles. Am J Physiol 263: H613–621.

34. Stones R, Calaghan SC, Billeter R, et al. (2007) Transmural variations in gene expression of stretch-modulated proteins in the rat left ventricle. Pflugers Arch 454: 545–549.

35. Taggart P (1996) Mechano-electric feedback in the human heart. Cardiovasc Res 32: 38–43.

36. Tan JH, Liu W, Saint DA (2004) Differential expression of the mechanosensitive potassium channel TREK-1 in epicardial and endocardial myocytes in rat ventricle. Exp Physiol 89:237–242.

37. Tan JH, Liu W, Saint DA (2002) Trek-like potassium channels in rat cardiac ventricular myocytes are activated by intracellular ATP. J Membr Biol 185: 201–207.

38. Tavi P, Han C, Weckstrom M (1998) Mechanisms of stretch-induced changes in [Ca2+]i in rat atrial myocytes: role of increased troponin C affinity and stretch-activated ion channels. Circ Res83: 1165–1177.

39. Todaka K, Ogino K, Gu A, et al. (1998) Effect of ventricular stretch on contractile strength, calcium transient, and cAMP in intact canine hearts. Am J Physiol 274: H990–1000.

40. Volk T, Nguyen TH, Schultz JH, et al. (1999) Relationship between transient outward K+ current and Ca2+ influx in rat cardiac myocytes of endo- and epicardial origin. J Physiol 519 Pt 3:841–850.

41. White E, Boyett MR, Orchard CH (1995) The effects of mechanical loading and changes of length on single guinea-pig ventricular myocytes. J Physiol 482 ( Pt 1): 93–107.

42. Wilhelm J, Kondratev D, Christ A, et al. (2006) Stretch induced accumulation of total Ca and Na in cytosol and nucleus: a comparison between cardiac trabeculae and isolated myocytes. Can J Physiol Pharmacol 84: 487–498.

43. Zabel M, Koller BS, Sachs F, et al. (1996) Stretch-induced voltage changes in the isolated beating heart: importance of the timing of stretch and implications for stretch-activated ion channels. Cardiovasc Res 32: 120–130.

Copyright Info: © 2014, David A. Saint, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (

Download full text in PDF

Export Citation

Article outline

Show full outline
Copyright © AIMS Press All Rights Reserved