Telocytes pp 241-251 | Cite as

Myocardial Telocytes: A New Player in Electric Circuitry of the Heart

  • Winston Shim
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 913)


The heart is an electrically conducting organ with networked bioelectric currents that transverse a large segment of interstitial space interspersed with the muscular parenchyma. Non-excitable connective cells in the interstitial space contributed importantly to many structural, biochemical, and physiological activities of cardiac homeostasis. However, contribution of interstitial cells in the cardiac niche has long been neglected. Telocyte is recently recognized as a distinct class of interstitial cell that resides in a wide array of tissues including in the epicardium, myocardium, and endocardium of the heart. They are increasingly described to conduct ionic currents that may have significant implications in bioelectric signaling. In this review, we highlight the significance of telocytes in such connectivity and conductivity within the interstitial bioelectric network in tissue homeostasis.


Interstitial cells Cardiac telocytes Bioelectric coupling Ion channels 



This work was supported by the National Research Foundation Singapore (NRF-CRP-2008-02), Goh Foundation Gift (Singapore)/Duke-NUS Medical School (GCR/2013/008, GCR/2013/010, and GCR/2013/011), and Biomedical Research Council, Singapore (BMRC13/1/96/19/86).


  1. 1.
    Levin M. Endogenous bioelectrical networks store non-genetic patterning information during development and regeneration. J Physiol. 2014;592(Pt 11):2295–305.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Levin M. Molecular bioelectricity in developmental biology: new tools and recent discoveries: control of cell behavior and pattern formation by transmembrane potential gradients. Bioessays. 2012;34(3):205–17.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Edelstein L, Smythies J. The role of telocytes in morphogenetic bioelectrical signaling: once more unto the breach. Front Mol Neurosci. 2014;7:41.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Camelliti P, Green CR, LeGrice I, et al. Fibroblast network in rabbit sinoatrial node: structural and functional identification of homogeneous and heterogeneous cell coupling. Circ Res. 2004;94(6):828–35.CrossRefPubMedGoogle Scholar
  5. 5.
    Gaudesius G, Miragoli M, Thomas SP, et al. Coupling of cardiac electrical activity over extended distances by fibroblasts of cardiac origin. Circ Res. 2003;93(5):421–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Sachse FB, Moreno AP, Abildskov JA. Electrophysiological modeling of fibroblasts and their interaction with myocytes. Ann Biomed Eng. 2008;36(1):41–56.CrossRefPubMedGoogle Scholar
  7. 7.
    Popescu LM, Gherghiceanu M, Manole CG, et al. Cardiac renewing: interstitial Cajal-like cells nurse cardiomyocyte progenitors in epicardial stem cell niches. J Cell Mol Med. 2009;13(5):866–86.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kostin S. Myocardial telocytes: a specific new cellular entity. J Cell Mol Med. 2010;14(7):1917–21.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gherghiceanu M, Manole CG, Popescu LM. Telocytes in endocardium: electron microscope evidence. J Cell Mol Med. 2010;14(9):2330–4.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kostin S, Popescu LM. A distinct type of cell in myocardium: interstitial Cajal-like cells (ICLCs). J Cell Mol Med. 2009;13(2):295–308.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Cretoiu SM, Cretoiu D, Marin A, et al. Telocytes: ultrastructural, immunohistochemical and electrophysiological characteristics in human myometrium. Reproduction. 2013;145(4):357–70.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Rosenbaum ST, Svalo J, Nielsen K, et al. Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium. J Cell Mol Med. 2012;16(12):3001–8.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Parsons SP, Huizinga JD. Transient outward potassium current in ICC. Am J Physiol Gastrointest Liver Physiol. 2010;298(3):G456–66.CrossRefPubMedGoogle Scholar
  14. 14.
    Si X, Huang L, Gong Y, et al. Role of calcium in activation of hyperpolarization-activated cyclic nucleotide-gated channels caused by cholecystokinin octapeptide in interstitial cells of cajal. Digestion. 2012;85(4):266–75.CrossRefPubMedGoogle Scholar
  15. 15.
    Zheng Y, Cretoiu D, Yan G, et al. Comparative proteomic analysis of human lung telocytes with fibroblasts. J Cell Mol Med. 2014;18(4):568–89.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Popescu LM, Manole CG, Gherghiceanu M, et al. Telocytes in human epicardium. J Cell Mol Med. 2010;14(8):2085–93.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Parajuli SP, Soder RP, Hristov KL, et al. Pharmacological activation of small conductance calcium-activated potassium channels with naphtho[1,2-d]thiazol-2-ylamine decreases guinea pig detrusor smooth muscle excitability and contractility. J Pharmacol Exp Ther. 2012;340(1):114–23.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zheng Y, Li H, Manole CG, et al. Telocytes in trachea and lungs. J Cell Mol Med. 2011;15(10):2262–8.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Popescu LM, Manole E, Serboiu CS, et al. Identification of telocytes in skeletal muscle interstitium: implication for muscle regeneration. J Cell Mol Med. 2011;15(6):1379–92.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zheng Y, Bai C, Wang X. Telocyte morphologies and potential roles in diseases. J Cell Physiol. 2012;227(6):2311–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Nguyen BL, Fishbein MC, Chen LS, et al. Histopathological substrate for chronic atrial fibrillation in humans. Heart Rhythm. 2009;6(4):454–60.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Mandache E, Gherghiceanu M, Macarie C, et al. Telocytes in human isolated atrial amyloidosis: ultrastructural remodelling. J Cell Mol Med. 2010;14(12):2739–47.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Hinescu ME, Popescu LM. Interstitial Cajal-like cells (ICLC) in human atrial myocardium. J Cell Mol Med. 2005;9(4):972–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Hinescu ME, Gherghiceanu M, Mandache E, et al. Interstitial Cajal-like cells (ICLC) in atrial myocardium: ultrastructural and immunohistochemical characterization. J Cell Mol Med. 2006;10(1):243–57.CrossRefPubMedGoogle Scholar
  25. 25.
    Gherghiceanu M, Popescu LM. Heterocellular communication in the heart: electron tomography of telocyte-myocyte junctions. J Cell Mol Med. 2011;15(4):1005–11.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Bani D, Formigli L, Gherghiceanu M, et al. Telocytes as supporting cells for myocardial tissue organization in developing and adult heart. J Cell Mol Med. 2010;14(10):2531–8.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Popescu LM, Faussone-Pellegrini MS. TELOCYTES – a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTES. J Cell Mol Med. 2010;14(4):729–40.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gherghiceanu M, Popescu LM. Cardiac telocytes – their junctions and functional implications. Cell Tissue Res. 2012;348(2):265–79.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Gittenberger-de Groot AC, Winter EM, Poelmann RE. Epicardium-derived cells (EPDCs) in development, cardiac disease and repair of ischemia. J Cell Mol Med. 2010;14(5):1056–60.PubMedGoogle Scholar
  30. 30.
    Nielsen MS, Axelsen LN, Sorgen PL, et al. Gap junctions. Compr Physiol. 2012;2(3):1981–2035.PubMedGoogle Scholar
  31. 31.
    Smythies J, Edelstein L. Telocytes, exosomes, gap junctions and the cytoskeleton: the makings of a primitive nervous system? Front Cell Neurosci. 2014;7:278.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Sheng J, Shim W, Lu J, et al. Electrophysiology of human cardiac atrial and ventricular telocytes. J Cell Mol Med. 2014;18(2):355–62.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Cretoiu SM, Radu BM, Banciu A, et al. Isolated human uterine telocytes: immunocytochemistry and electrophysiology of T-type calcium channels. Histochem Cell Biol. 2015;143(1):83–94.CrossRefPubMedGoogle Scholar
  34. 34.
    Mou Y, Wang Y, Li J, et al. Immunohistochemical characterization and functional identification of mammary gland telocytes in the self-assembly of reconstituted breast cancer tissue in vitro. J Cell Mol Med. 2013;17(1):65–75.CrossRefPubMedGoogle Scholar
  35. 35.
    Xiao J, Wang F, Liu Z, et al. Telocytes in liver: electron microscopic and immunofluorescent evidence. J Cell Mol Med. 2013;17(12):1537–42.Google Scholar
  36. 36.
    Miao Q, Shim W, Tee N, et al. iPSC-derived human mesenchymal stem cells improve myocardial strain of infarcted myocardium. J Cell Mol Med. 2014;18(8):1644–54.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ja KM, Miao Q, Zhen Tee NG, et al. iPSC-derived human cardiac progenitor cells improve ventricular remodelling via angiogenesis and interstitial networking of infarcted myocardium. J Cell Mol Med. 2015;20(2):323–32.Google Scholar
  38. 38.
    Zhao B, Liao Z, Chen S, et al. Intramyocardial transplantation of cardiac telocytes decreases myocardial infarction and improves post-infarcted cardiac function in rats. J Cell Mol Med. 2014;18(15):780–89.Google Scholar
  39. 39.
    Zhao B, Chen S, Liu J, et al. Cardiac telocytes were decreased during myocardial infarction and their therapeutic effects for ischaemic heart in rat. J Cell Mol Med. 2013;17(1):123–33.CrossRefPubMedGoogle Scholar
  40. 40.
    Richter M, Kostin S. The failing human heart is characterized by decreased numbers of telocytes as result of apoptosis and altered extracellular matrix composition. J Cell Mol Med. 2015;19(11):2597–606.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Weber KT, Sun Y, Bhattacharya SK, et al. Myofibroblast-mediated mechanisms of pathological remodelling of the heart. Nat Rev Cardiol. 2013;10(1):15–26.CrossRefPubMedGoogle Scholar
  42. 42.
    Popescu LM, Gherghiceanu M, Hinescu ME, et al. Insights into the interstitium of ventricular myocardium: interstitial Cajal-like cells (ICLC). J Cell Mol Med. 2006;10(2):429–58.CrossRefPubMedGoogle Scholar
  43. 43.
    Fertig ET, Gherghiceanu M, Popescu LM. Extracellular vesicles release by cardiac telocytes: electron microscopy and electron tomography. J Cell Mol Med. 2014;18(10):1938–43.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Popescu LM, Fertig ET, Gherghiceanu M. Reaching out: junctions between cardiac telocytes and cardiac stem cells in culture. J Cell Mol Med. 2015;20(2):370–80.Google Scholar
  45. 45.
    Cretoiu D, Hummel E, Zimmermann H, et al. Human cardiac telocytes: 3D imaging by FIB-SEM tomography. J Cell Mol Med. 2014;18(11):2157–64.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kohl P, Gourdie RG. Fibroblast-myocyte electrotonic coupling: does it occur in native cardiac tissue? J Mol Cell Cardiol. 2014;70:37–46.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Wang X, Veruki ML, Bukoreshtliev NV, et al. Animal cells connected by nanotubes can be electrically coupled through interposed gap-junction channels. Proc Natl Acad Sci U S A. 2010;107(40):17194–9.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    He K, Shi X, Zhang X, et al. Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes. Cardiovasc Res. 2011;92(1):39–47.CrossRefPubMedGoogle Scholar
  49. 49.
    Miragoli M, Gaudesius G, Rohr S. Electrotonic modulation of cardiac impulse conduction by myofibroblasts. Circ Res. 2006;98(6):801–10.CrossRefPubMedGoogle Scholar
  50. 50.
    Campeanu RA, Radu BM, Cretoiu SM, et al. Near-infrared low-level laser stimulation of telocytes from human myometrium. Lasers Med Sci. 2014;29(6):1867–74.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Zhu Y, Mucci A, Huizinga JD. Inwardly rectifying chloride channel activity in intestinal pacemaker cells. Am J Physiol Gastrointest Liver Physiol. 2005;288(4):G809–21.CrossRefPubMedGoogle Scholar
  52. 52.
    Zhu MH, Sung IK, Zheng H, et al. Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal. J Physiol. 2011;589(Pt 18):4565–82.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Lee H, Koh BH, Peri LE, et al. Functional expression of SK channels in murine detrusor PDGFR+ cells. J Physiol. 2013;591(Pt 2):503–13.CrossRefPubMedGoogle Scholar
  54. 54.
    Kim YC, Suzuki H, Xu WX, et al. Ca2+ -activated K+ current in freshly isolated c-Kit positive cells in guinea-pig stomach. J Korean Med Sci. 2009;24(3):384–91.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Hanna N, Cardin S, Leung TK, et al. Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failure. Cardiovasc Res. 2004;63(2):236–44.CrossRefPubMedGoogle Scholar
  56. 56.
    Burstein B, Libby E, Calderone A, et al. Differential behaviors of atrial versus ventricular fibroblasts: a potential role for platelet-derived growth factor in atrial-ventricular remodeling differences. Circulation. 2008;117(13):1630–41.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2016

Authors and Affiliations

  1. 1.National Heart Research Institute SingaporeSingaporeSingapore
  2. 2.Cardiovascular and Metabolic Disorders ProgramDuke-NUS Medical SchoolSingaporeSingapore

Personalised recommendations