Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1981 Nov 1;91(2):505–523. doi: 10.1083/jcb.91.2.505

Intercellular communication in normal and regenerating rat liver: a quantitative analysis

PMCID: PMC2111978  PMID: 7309793

Abstract

We have compared intercellular communication in the regenerating and normal livers of weanling rats. The electrophysiological studies were conducted at the edge of the liver, and we have found that here as elsewhere in the liver there is a dramatic decrease in the number and size of gap junctions during regeneration. The area of hepatocyte membrane occupied by gap junctions is reduced 100-fold 29-35 h after hepatectomy. By combining observations made with the scanning electron microscope with our freeze fracture data we have estimated the number of "communicating interfaces" (areas of contact between hepatocytes that include at least one gap junction) formed by hepatocytes in normal and regenerating liver. In normal liver a hepatocyte forms gap junctions with every hepatocyte it contacts (approximately 6). In regenerating liver a hepatocyte forms detectable gap junctions with, on average, only one other hepatocyte. Intercellular spread of fluorescent dye and electric current is reduced in regenerating as compared with normal liver. The incidence of electric coupling is reduced from 100% of hepatocyte pairs tested in control liver to 92% in regenerating liver. Analysis of the spatial dependence of electronic potentials indicates a substantial increase in intercellular resistance in regenerating liver. A quantitative comparison of our morphological and physiological data is complicated by tortuous pattern of current flow and by inhomogeneities in the liver during regeneration. Nevertheless we believe that our results are consistent with the hypothesis that gap junctions are aggregates of channels between cell interiors.

Full Text

The Full Text of this article is available as a PDF (2.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BARR L., DEWEY M. M., BERGER W. PROPAGATION OF ACTION POTENTIALS AND THE STRUCTURE OF THE NEXUS IN CARDIAC MUSCLE. J Gen Physiol. 1965 May;48:797–823. doi: 10.1085/jgp.48.5.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BUCHER N. L. REGENERATION OF MAMMALIAN LIVER. Int Rev Cytol. 1963;15:245–300. doi: 10.1016/s0074-7696(08)61119-5. [DOI] [PubMed] [Google Scholar]
  3. Barr L., Berger W., Dewey M. M. Electrical transmission at the nexus between smooth muscle cells. J Gen Physiol. 1968 Mar;51(3):347–368. doi: 10.1085/jgp.51.3.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bennett M. V., Trinkaus J. P. Electrical coupling between embryonic cells by way of extracellular space and specialized junctions. J Cell Biol. 1970 Mar;44(3):592–610. doi: 10.1083/jcb.44.3.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brink P. R., Dewey M. M. Nexal membrane permeability to anions. J Gen Physiol. 1978 Jul;72(1):67–86. doi: 10.1085/jgp.72.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Claret M., Coraboeuf E. Membrane potential of perfused and isolated rat liver. J Physiol. 1970 Sep;210(2):137P–138P. [PubMed] [Google Scholar]
  7. DEWEY M. M., BARR L. A STUDY OF THE STRUCTURE AND DISTRIBUTION OF THE NEXUS. J Cell Biol. 1964 Dec;23:553–585. doi: 10.1083/jcb.23.3.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Daniel E. E., Daniel V. P., Duchon G., Garfield R. E., Nichols M., Malhotra S. K., Oki M. Is the nexus necessary for cell-to-cell coupling of smooth muscle? J Membr Biol. 1976 Aug 26;28(2-3):207–239. doi: 10.1007/BF01869698. [DOI] [PubMed] [Google Scholar]
  9. Dreifuss J. J., Girardier L. Etude de la propagation de l'excitation dans le ventricule de rat au moyen de solutions hypertoniques. Pflugers Arch Gesamte Physiol Menschen Tiere. 1966;292(1):13–33. [PubMed] [Google Scholar]
  10. FURUKAWA T., FURSHPAN E. J. Two inhibitory mechanisms in the Mauthner neurons of goldfish. J Neurophysiol. 1963 Jan;26:140–176. doi: 10.1152/jn.1963.26.1.140. [DOI] [PubMed] [Google Scholar]
  11. Flagg-Newton J., Loewenstein W. R. Experimental depression of junctional membrane permeability in mammalian cell culture. A study with tracer molecules in the 300 to 800 Dalton range. J Membr Biol. 1979 Oct 5;50(1):65–100. doi: 10.1007/BF01868788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Friedmann N., Somlyo A. V., Somlyo A. P. Cyclic adenosine and guaosine monophosphates and gucagon: effect on liver membrane potentials. Science. 1971 Jan 29;171(3969):400–402. doi: 10.1126/science.171.3969.400. [DOI] [PubMed] [Google Scholar]
  13. Fry G. N., Devine C. E., Burnstock G. Freeze-fracture studies of nexuses between smooth muscle cells. Close relationship to sarcoplasmic reticulum. J Cell Biol. 1977 Jan;72(1):26–34. doi: 10.1083/jcb.72.1.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gabella G., Blundell D. Nexuses between the smooth muscle cells of the guinea-pig ileum. J Cell Biol. 1979 Jul;82(1):239–247. doi: 10.1083/jcb.82.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gabella G. Intercellular junctions between circular and longitudinal intestinal muscle layers. Z Zellforsch Mikrosk Anat. 1972;125(2):191–199. doi: 10.1007/BF00306788. [DOI] [PubMed] [Google Scholar]
  16. Gilula N. B., Reeves O. R., Steinbach A. Metabolic coupling, ionic coupling and cell contacts. Nature. 1972 Feb 4;235(5336):262–265. doi: 10.1038/235262a0. [DOI] [PubMed] [Google Scholar]
  17. Goodenough D. A. The structure and permeability of isolated hepatocyte gap junctions. Cold Spring Harb Symp Quant Biol. 1976;40:37–43. doi: 10.1101/sqb.1976.040.01.006. [DOI] [PubMed] [Google Scholar]
  18. Graf J., Petersen O. H. Cell membrane potential and resistance in liver. J Physiol. 1978 Nov;284:105–126. doi: 10.1113/jphysiol.1978.sp012530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Haylett D. G., Jenkinson D. H. Effects of noradrenaline on potassium reflux, membrane potential and electrolyte levels in tissue slices prepared from guinea-pig liver. J Physiol. 1972 Sep;225(3):721–750. doi: 10.1113/jphysiol.1972.sp009966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hudspeth A. J., Corey D. P. Controlled bending of high-resistance glass microelectrodes. Am J Physiol. 1978 Jan;234(1):C56–C57. doi: 10.1152/ajpcell.1978.234.1.C56. [DOI] [PubMed] [Google Scholar]
  21. Johnson R., Hammer M., Sheridan J., Revel J. P. Gap junction formation between reaggregated Novikoff hepatoma cells. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4536–4540. doi: 10.1073/pnas.71.11.4536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. LOEWENSTEIN W. R., KANNO Y. STUDIES ON AN EPITHELIAL (GLAND) CELL JUNCTION. I. MODIFICATIONS OF SURFACE MEMBRANE PERMEABILITY. J Cell Biol. 1964 Sep;22:565–586. doi: 10.1083/jcb.22.3.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Larsen W. J., Azarnia R., Loewenstein W. R. Intercellular communication and tissue growth: IX. Junctional membrane structure of hybrids between communication-competent and communication-incompetent cells. J Membr Biol. 1977 Jun 3;34(1):39–54. doi: 10.1007/BF01870292. [DOI] [PubMed] [Google Scholar]
  24. Loewenstein W. R. Junctional intercellular communication and the control of growth. Biochim Biophys Acta. 1979 Feb 4;560(1):1–65. doi: 10.1016/0304-419x(79)90002-7. [DOI] [PubMed] [Google Scholar]
  25. Loewenstein W. R., Penn R. D. Intercellular communication and tissue growth. II. Tissue regeneration. J Cell Biol. 1967 May;33(2):235–242. doi: 10.1083/jcb.33.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Makowski L., Caspar D. L., Phillips W. C., Goodenough D. A. Gap junction structures. II. Analysis of the x-ray diffraction data. J Cell Biol. 1977 Aug;74(2):629–645. doi: 10.1083/jcb.74.2.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Motta P., Porter K. R. Structure of rat liver sinusoids and associated tissue spaces as revealed by scanning electron microscopy. Cell Tissue Res. 1974 Mar 29;148(1):111–125. doi: 10.1007/BF00224322. [DOI] [PubMed] [Google Scholar]
  28. Pappas G. D., Asada Y., Bennett M. V. Morphological correlates of increased coupling resistance at an electrotonic synapse. J Cell Biol. 1971 Apr;49(1):173–188. doi: 10.1083/jcb.49.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Penn R. D. Ionic communication between liver cells. J Cell Biol. 1966 Apr;29(1):171–174. doi: 10.1083/jcb.29.1.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Peskoff A. Electric potential in cylindrical syncytia and muscle fibers. Bull Math Biol. 1979;41(2):183–192. doi: 10.1007/BF02460877. [DOI] [PubMed] [Google Scholar]
  31. Peskoff A. Electric potential in three-dimensional electrically syncytial tissues. Bull Math Biol. 1979;41(2):163–181. doi: 10.1007/BF02460876. [DOI] [PubMed] [Google Scholar]
  32. Potter D. D., Furshpan E. J., Lennox E. S. Connections between cells of the developing squid as revealed by electrophysiological methods. Proc Natl Acad Sci U S A. 1966 Feb;55(2):328–336. doi: 10.1073/pnas.55.2.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Revel J. P., Yee A. G., Hudspeth A. J. Gap junctions between electrotonically coupled cells in tissue culture and in brown fat. Proc Natl Acad Sci U S A. 1971 Dec;68(12):2924–2927. doi: 10.1073/pnas.68.12.2924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rose B., Simpson I., Loewenstein W. R. Calcium ion produces graded changes in permeability of membrane channels in cell junction. Nature. 1977 Jun 16;267(5612):625–627. doi: 10.1038/267625a0. [DOI] [PubMed] [Google Scholar]
  35. Schanne O., Coraboeuf E. Potential and resistance measurements of rat liver cells in situ. Nature. 1966 Jun 25;210(5043):1390–1391. doi: 10.1038/2101390a0. [DOI] [PubMed] [Google Scholar]
  36. Sheridan J. D. Electrical coupling between fat cells in newt fat body and mouse brown fat. J Cell Biol. 1971 Sep;50(3):795–803. doi: 10.1083/jcb.50.3.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Stewart W. W. Functional connections between cells as revealed by dye-coupling with a highly fluorescent naphthalimide tracer. Cell. 1978 Jul;14(3):741–759. doi: 10.1016/0092-8674(78)90256-8. [DOI] [PubMed] [Google Scholar]
  38. Unwin P. N., Zampighi G. Structure of the junction between communicating cells. Nature. 1980 Feb 7;283(5747):545–549. doi: 10.1038/283545a0. [DOI] [PubMed] [Google Scholar]
  39. Vial J., Porter K. R. Scanning microscopy of dissociated tissue cells. J Cell Biol. 1975 Nov;67(2PT1):345–360. doi: 10.1083/jcb.67.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Weibel E. R., Stäubli W., Gnägi H. R., Hess F. A. Correlated morphometric and biochemical studies on the liver cell. I. Morphometric model, stereologic methods, and normal morphometric data for rat liver. J Cell Biol. 1969 Jul;42(1):68–91. doi: 10.1083/jcb.42.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wondergem R., Harder D. R. Membrane potential measurements during rat liver regeneration. J Cell Physiol. 1980 Feb;102(2):193–197. doi: 10.1002/jcp.1041020210. [DOI] [PubMed] [Google Scholar]
  42. Yancey S. B., Easter D., Revel J. P. Cytological changes in gap junctions during liver regeneration. J Ultrastruct Res. 1979 Jun;67(3):229–242. doi: 10.1016/s0022-5320(79)80024-6. [DOI] [PubMed] [Google Scholar]
  43. Yee A. G., Revel J. P. Loss and reappearance of gap junctions in regenerating liver. J Cell Biol. 1978 Aug;78(2):554–564. doi: 10.1083/jcb.78.2.554. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES