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Mechanically induced potentials in atrial fibroblasts from rat hearts are sensitive to hypoxia/reoxygenation

  • Cardiovascular System
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Abstract

Membrane potential changes of atrial fibroblasts in response to mechanical stress have been considered to modulate the rhythmic electrical activity of healthy hearts. Our recent findings suggest that cardiac arrhythmia after infarction is related to enhanced susceptibility of the fibroblasts to physical stretch. In this study, we analysed the effect of hypoxia/reoxygenation, which are major components of tissue ischemia/reperfusion, on the membrane potential of atrial fibroblasts. Intracellular microelectrode recordings were performed together with isometric force measurements on isometrically contracting right atrial tissue preparations from adult rats. Lowering the oxygen tension in the perfusate from 80 kPa to 3.5 kPa reduced active force development and decreased the resting membrane potential of the cardiac fibroblasts from −23±5 mV to −5±2 mV (n=35). Application of gadolinium (40 μM) to inhibit non-selective cation channels prevented hypoxia-induced membrane depolarization of the fibroblasts. Reoxygenation of the myocardial tissue resulted in a transient increase of the resting membrane potential to maximally −60±8 mV. These findings indicate that transmembrane currents in atrial fibroblasts are sensitive to changes in tissue oxygenation. In conclusion, altered electro-mechanical function of the ischemic heart may possibly involve changes of the membrane potential of the cardiac fibroblasts.

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References

  1. Camelliti P, Kohl P, Green C (2002) Myocyte/non-myocyte interactions in the heart: clues to an alternative mechanosensor for cardiac MEF. In: Proceedings of the Physiological Society, University of Leeds, 10–12 September, 21P

  2. Duncan CJ (1978) Role of intracellular calcium in promoting muscle damage: a strategy for controlling the dystrophic condition. Experimentia 34:1531–1535

    CAS  Google Scholar 

  3. Dzau VJ (1993) Local contractile and growth modulators in the myocardium. Clin Cardiol 16 [Suppl 2]:II5–II9

    Google Scholar 

  4. Eghbali M (1992) Cardiac fibroblasts: function, regulation of gene expression and phenotypic modulation. Basic Res Cardiol 87:183–189

    CAS  PubMed  Google Scholar 

  5. French AS, Stockbridge LL (1988) Potassium channels in human and avian fibroblasts. Proc R Soc Lond B 232:395–412

    CAS  PubMed  Google Scholar 

  6. Jennings RB, Reimer KA, Steenbergen C (1985) Myocardial ischemia and reperfusion: role of calcium. In: Parratt JR (ed) Control and manipulation of calcium movement. Raven, New York, pp 273–302

  7. Kamkin A, Kiseleva I, Isenberg G (2003) Activation and inactivation of a non-selective cation conductance by local mechanical deformation of acutely isolated cardiac fibroblasts. Cardiovasc Res (in press)

  8. Kamkin A, Kiseleva I, Wagner KD, Lammerich A, Bohm J, Persson PB, Günther J (1999) Mechanically induced potentials in fibroblasts from human right atrium. Exp Physiol 84:347–356

    Article  CAS  PubMed  Google Scholar 

  9. Kamkin A, Kiseleva I, Wagner KD, Pylaev A, Leiterer KP, Theres H, Scholz H, Günther J, Isenberg G (2002) A possible role for atrial fibroblasts in postinfarction bradycardia. Am J Physiol 282:H842–H849

    CAS  Google Scholar 

  10. Kiseleva I, Kamkin A, Kohl P, Lab MJ (1996) Calcium and mechanically induced potentials in fibroblasts of rat atrium. Cardiovasc Res 32:98–111

    Article  CAS  PubMed  Google Scholar 

  11. Kiseleva I, Kamkin A, Pylaev A, Kondratjev D, Leiterer KP, Theres H, Wagner KD, Persson PB, Günther J (1998) Electrophysiological properties of mechanosensitive atrial fibroblasts from chronic infarcted rat heart. J Mol Cell Cardiol 30:1083–1093

    Article  CAS  PubMed  Google Scholar 

  12. Kohl P (1995) Mechano-electric feedback impact on heart rhythm. Futura 4:240–252

    Google Scholar 

  13. Kohl P, Kamkin A, Kiseleva I, Noble D (1994) Mechanosensitive fibroblasts in the sino-atrial node region of rat heart: interaction with cardiomyocytes and possible role. Exp Physiol 79:943–956

    CAS  PubMed  Google Scholar 

  14. Kohl P, Kamkin A, Kiseleva I, Streubel T (1992) Mechanosensitive cells in the atrium of frog heart. Exp Physiol 77:213–216

    CAS  PubMed  Google Scholar 

  15. Kohl P, Noble D (1996) Mechanosensitive connective tissue: potential influence on heart rhythm. Cardiovasc Res 32:62–68

    Article  CAS  PubMed  Google Scholar 

  16. Lab MJ (1996) Mechanoelectric feedback (transduction) in heart: concepts and implication. Cardiovasc Res 32:3–14

    CAS  PubMed  Google Scholar 

  17. Lammerich A, Bohm J, Schimke I, Wagner KD, Storch E, Günther J (1996) Effects of hypoxia, simulated ischemia and reoxygenation on the contractile function of human atrial trabeculae. Mol Cell Biochem 160/161:143–151

    Google Scholar 

  18. Naccarella F, Lepera G, Rolli A (2000) Arrhythmic risk stratification of post-myocardial infarction patients. Curr Opin Cardiol 15:1–6

    Article  CAS  PubMed  Google Scholar 

  19. Nayler WG, Poole-Wison PA, Williams A (1979) Hypoxia and calcium. J Mol Cell Cardiol 11:683–706

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Okada Y, Oiki T, Ohno-Shosaku S, Ueda S, Yada T (1986) Intracellular Ca2+ and calmodulin regulate K+ conductance in cultured fibroblasts. Biomed Res 7S:73–78

    Google Scholar 

  22. Rook MB, van Ginneken ACG, de Jonge B, El Aoumari A, Gros D, Jongsma HJ (1992) Differences in gap junction channels between cardiac myocytes, fibroblasts, and heterologous pairs. Am J Physiol 263:C959–C977

    CAS  PubMed  Google Scholar 

  23. Underwood RD, Sra J, Akhtar M (1997) Evaluation and treatment strategies in patients at high risk of sudden death post myocardial infarction. Clin Cardiol 20:753–758

    CAS  PubMed  Google Scholar 

  24. Wagner KD, Theres H, Born A, Strube S, Wunderlich N, Pfitzer G, Baumann G, Günther J (1997) Contractile function of papillary muscle from rats with different infarct size after β-adrenergic blockade and ACE-inhibition. J Mol Cell Cardiol 29:2941–2951

    Article  CAS  PubMed  Google Scholar 

  25. Ward H, White E (1994) Reduction in the contraction and intracellular calcium transient of single rat ventricular myocytes by gadolinium and the attenuation of these effects by extracellular NaH2PO4. Exp Physiol 79:107–110

    CAS  PubMed  Google Scholar 

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Acknowledgements

This study was financially supported by grants from the Humboldt-University of Berlin and the Alexander von Humboldt-Stiftung. A.K. was a fellow of the Alexander von Humboldt-Stiftung, and I.K. received a travel grant from the Humboldt-University.

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Authors and Affiliations

  1. Johannes-Müller-Institut für Physiologie, Humboldt-Universität Charité, Tucholskystrasse 2, 10117 , Berlin, Germany

    Kay-Dietrich Wagner

  2. Johannes-Müller-Institut für Physiologie, Medizinische Fakultät Charité, Humboldt-Universität, Tucholskystrasse 2, 10117 , Berlin, Germany

    Andre Kamkin, Irina Kiseleva, Kay-Dietrich Wagner, Ilja Lozinsky, Joachim Günther & Holger Scholz

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  1. Andre Kamkin
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  2. Irina Kiseleva
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  3. Kay-Dietrich Wagner
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  4. Ilja Lozinsky
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  5. Joachim Günther
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  6. Holger Scholz
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Correspondence to Kay-Dietrich Wagner.

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Kamkin, A., Kiseleva, I., Wagner, KD. et al. Mechanically induced potentials in atrial fibroblasts from rat hearts are sensitive to hypoxia/reoxygenation. Pflugers Arch - Eur J Physiol 446, 169–174 (2003). https://doi.org/10.1007/s00424-003-1032-0

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  • DOI: https://doi.org/10.1007/s00424-003-1032-0

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