The Perinodal Astrocyte: Functional and Developmental Considerations

  • Stephen G. Waxman
Part of the Altschul Symposia Series book series (ALSS, volume 2)


Since perinodal astrocytes were first described more than two decades ago (Hildebrand 1971a,b), the presence of astrocyte processes which contact the node of Ranvier has been documented in numerous CNS tracts and in many species (Waxman and Black 1984; Hildebrand and Waxman 1984; Raine 1984; Sims et al. 1985; Bodega et al. 1987; Sims et al. 1991). Perinodal astrocytes are associated with myelinated axons in a highly specific manner at the nodes of Ranvier. Thus, each myelinated axon in the CNS is contacted by numerous perinodal astrocytes. Despite the ubiquity of these specialized cells, however, their functions remain obscure. Over the past few years, our laboratory has carried out ultrastructural, immunocytochemical, electrophysiological, and biophysical studies on astrocytes in white matter (see e.g., Black et al. 1989a,b; Minturn et al. 1990, 1992; Sontheimer et al. 1991a,b,c) which have begun to delineate the properties of these cells. Several other laboratories have also provided new information that may be relevant to the properties of perinodal astrocytes (e.g., Nowak et al. 1987; Barres et al. 1988, 1989, 1990; Bevan et al. 1985; Gray and Ritchie 1986; Ransom and Carlini 1986). The present chapter will briefly review some of the more recent studies from these laboratories which provide information about astrocyte properties, and will examine the question, What do perinodal astrocytes do?


Sodium Channel Retinal Nerve Fiber Layer Myelinated Axon Axon Membrane Retinal Glial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ard, M.D., and Faissner, A., 1991, Components of astrocytic extracellular matrix are regulated by contact with axons, Ann. NYAcad. Sci. 633: 566–570.CrossRefGoogle Scholar
  2. Ariyasu, R.G., Nichol, J.A., and Ellisman, M.K., 1985, Localization of Na/K ATPase in multiple cell types of murine nervous system with antibodies raised against the enzyme from kidney. J. Neurosci. 5: 2581–2596.PubMedGoogle Scholar
  3. Barres, B.A., Chun, L.L.Y., and Corey, D.P., 1988, Ion channel expression by white matter glia: I. Type 2 astrocytes and oligodendrocytes, Glia 1: 10–30.PubMedCrossRefGoogle Scholar
  4. Barres, B.A., Chun, L.L.Y., and Corey, D.P., 1989, Glial and neuronal forms of the voltage-sensitive sodium channel, Neuron 2: 1375–1388.PubMedCrossRefGoogle Scholar
  5. Barres, B.A., Koroshetz, W.J., Chun, L.L.Y., and Corey, D.P., 1990, Ion channel expression by white matter glia: The type-1 astrocyte, Neuron,in press.Google Scholar
  6. Barres, B.A., 1991, New roles for glia, J. Neurosci. 11: 3685–3694.PubMedGoogle Scholar
  7. Bevan, S.S.Y. Chiu, P.T.A. Gray, and J.M. Ritchie. 1985. The presence of voltage-gated sodium, potassium and chloride channels in rat cultured astrocytes. Proc. Roy. Soc. (Lond.) B 225: 299–313.CrossRefGoogle Scholar
  8. Birch, B.D., Kocsis, J.D., DiGregorio, F., Bhisitkul, R.B., and Waxman, S.G., 1991, A voltage-and time-dependent rectification in rat dorsal spinal root axons, J. Neurophysiol., 66: 719–730.PubMedGoogle Scholar
  9. Black, J.A., Foster, R.E., and Waxman, S.G., 1982, Rat optic nerve: freeze-fracture studies during development of myelinated axons, Brain Research 250: 1–10.PubMedCrossRefGoogle Scholar
  10. Black, J.A., and Waxman, S.G., 1988, The perinodal astrocyte, Glia 1: 169–183.PubMedCrossRefGoogle Scholar
  11. Black, J.A., Friedman, B., Waxman, S.G., Elmer, L.W., and Angelides, K.J., 1989a, Immunoultrastructural localization of sodium channels at nodes of Ranvier and perinodal astrocytes in rat optic nerve, Proc. Roy. Soc. (Lond.) B 238: 39–51.CrossRefGoogle Scholar
  12. Black, J.A., Waxman, S.G., Friedman, B., Elmer, L.W., and Angelides, K.J., 1989b, Sodium channels in astrocytes of rat optic nerve in situ: immun-electron microscopic studies, Glia 2: 353–369.PubMedCrossRefGoogle Scholar
  13. Black, J.A., Kocsis, J.D., and Waxman, S.G., 1990, Ion channel organization of the myelinated fiber, Trends Neurosci. 13: 48–54.PubMedCrossRefGoogle Scholar
  14. Black, J.A., Felts, P., Smith, K.J., Kocsis, J.D., and Waxman, S.G., 1991, Distribution of sodium channels in chronically demyelinated spinal cord axons: immun-ultrastructural localization and electrophysiological observations, Brain Research 544: 59–70.PubMedCrossRefGoogle Scholar
  15. Blakemore, W.F., and Smith, K.J., 1983, Node-like axonal specialization along demyelinated central nerve fibres: Ultrastructural observations, Acta Neuropathol. 60: 291–296.PubMedCrossRefGoogle Scholar
  16. Bodega, G., Suarez, I., and Fernandez, B., 1987, Fine structural relationships between astrocytes and the node of Ranvier in the amphibian and reptile spinal cord, Neurosci. Leu. 80: 7–10.CrossRefGoogle Scholar
  17. Brew, H., Gray, P.T.A., Mobbs, P., and Attwell, D. 1986, Endfeet of retinal glial cells have higher densities of ion channels that mediate K buffering, Nature 324: 466–468.PubMedCrossRefGoogle Scholar
  18. Elmer, L.W., Black, J.A., Waxman, S.G., and Angelides, K.J., 1990, The voltage-dependent sodium channel in mammalian CNS and PNS: Antibody characterization and immunocytochemical localization, Brain Research 532: 222–231.PubMedCrossRefGoogle Scholar
  19. Eng, L.F., DAmelio, F.E., and Smith, M.E., 1989, Dissociation of GFAP intermediate filaments in EAE: observations in the lumbar spinal cord, Glia 2: 308–317.PubMedCrossRefGoogle Scholar
  20. Eng, D.L., Gordon, T.R., Kocsis, J.D., and Waxman, S.G., 1988, Development of 4-AP and TEA sensitivities in mammalian myelinated nerve fibers, J. Neurophysiol. 60: 2168–2179.PubMedGoogle Scholar
  21. Eng, D.L., Gordon, T.R., Kocsis, J.D., and Waxman, S.G., 1990, Current-clamp analysis of a time dependent rectification in rat optic nerve, J. Physiol. (Lond.) 421: 185–202.Google Scholar
  22. ffrench-Constant, C., Miller, R.H., Kruse, J., Schachner, M., and Raff, M.D., 1986, Molecular specialization of astrocyte processes at nodes of Ranvier in rat optic nerve, J. Cell Biol. 102: 844–852.PubMedCrossRefGoogle Scholar
  23. Friedman, B., Black, J.A., Hockfield, S., Waxman, S.G., and Ransom, B.R., 1989, Antigenic abnormalities in fiber tract astrocytes of myelin-deficient rats: an immunocytochemical study in the olfactory cortex, Devel. Neuroscience 11: 99–111.CrossRefGoogle Scholar
  24. Gordon, T.R., Kocsis, J.D., and Waxman, S.G., 1990, Electrogenic pump (Na+/K+-ATPase) activity in rat optic nerve, Neuroscience 37: 829–837.PubMedCrossRefGoogle Scholar
  25. Gray, P.T.A., and Ritchie, J.M., 1985, Ion channels in Schwann and glial cells. Trends Neurosci. 8: 411–415.CrossRefGoogle Scholar
  26. Gray, P.T.A., and Ritchie, J.M., 1986, A voltage-gated chloride conductance in rat cultured astrocytes, Proc. Roy. Soc. (Lond.) B 228: 267–288.CrossRefGoogle Scholar
  27. Hildebrand, C., 1971a, Ultrastructural and light-microscopic studies of the nodal region in large myelinated fibres of the adult feline spinal cord white matter, Acta Physiol. Scand. 364: 43–71.Google Scholar
  28. Hildebrand, C., 197 lb, Ultrastructural and light-microscopic studies of the developing feline spinal cord white matter. I. The nodes of Ranvier, Acta Physiol. Scand. 364: 81–101.Google Scholar
  29. Hildebrand, C., and Waxman, S.G., 1983, Regional node-like membrane specializations in nonmyelinated axons of rat retinal nerve fiber layer, Brain Research 258: 23–32.CrossRefGoogle Scholar
  30. Hildebrand, C., and Waxman, S.G., 1984, Postnatal differentiation of rat optic nerve fibers: Electron microscopic observations on the development of nodes of Ranvier and axoglial relations, J. Comp. Neurol. 224: 25–37.PubMedCrossRefGoogle Scholar
  31. Jendelov’a, P., and Sykov’a, E., 1991, Role of glia in potassium and pH homeostasis in the neonatal rat spinal cord, Glia 4: 56–63.CrossRefGoogle Scholar
  32. Kruse, J.R., Keilhauer, G., Faissner, A., Timpl, R., and Schachner, M., 1985, The J1 glycoprotein-a novel nervous system cell adhesion molecule of the L2/HNK-1 family, Nature 316: 146–148.PubMedCrossRefGoogle Scholar
  33. Landon, D.N., and Langley, O.K., 1971, The local chemical environment of the node of Ranvier. A study of cation binding, J. Anat. 108: 419–432.PubMedGoogle Scholar
  34. Landon, D.N., and Hall, S., 1976, The myelinated fiber, in: “The Peripheral Nerve”, D.N. Landon, ed., Chapman and Hall, London.Google Scholar
  35. McMahan, U.J., 1990, The agrin hypothesis, Cold Spring Harbor Symp. Quant. Biol. 55:407–418. Magill-Solc, C., and McMahan, U.J., 1990, Synthesis and transport of agrin-like molecules in motor neurons, J. Exp. Res. 153: 1–14.Google Scholar
  36. Mintum, J.E., Black, J.A., Angelides, K.J., and Waxman, S.G., 1990, Sodium channel expression detected with antibody 7493 in A2B5+ and A2B5- astrocytes from rat optic nerve in vitro, Glia 3: 358–368.CrossRefGoogle Scholar
  37. Minturn, J.E., Sontheimer, H., Black, J.A., Ransom, B.R., and Waxman, S.G., 1992, Sodium channel expression in optic nerve astrocytes chronically-deprived of axonal contact, Glia,in press.Google Scholar
  38. Newman, E.A., 1986, High potassium conductance in astrocyte endfeet, Science 233: 453–454.PubMedCrossRefGoogle Scholar
  39. Newman, E.A., 1987, Distribution of potassium conductance in mammalian Muller (glial) cells: A comparative study, J. Neurosci. 7: 2423–2432.PubMedGoogle Scholar
  40. Newman, E.A., Frambach, D.A., and Odette, L.L., 1984, Control of extracellular potassium levels by retinal glial cell K siphoning, Science 225: 1174–1175.PubMedCrossRefGoogle Scholar
  41. Nowak, L., Ascher, P., and Berwald-Netter, Y., 1987, Ionic channels in mouse astrocytes in culture, J. Neurosci. 7: 101–109.PubMedGoogle Scholar
  42. Orkand, R.K., Nicholls, J.G., and Kuffler, S.W., 1966, Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia, J. Neurophysiol. 29: 788–806.PubMedGoogle Scholar
  43. Quick, D.C., and Waxman, S.G., 1978, Evidence for inorganic phosphate binding at nodes of Ranvier in peripheral nerve, J. Neurol. Sci. 33: 207–211.CrossRefGoogle Scholar
  44. Raine, C.S., 1984, On the association between perinodal astrocyte processes and nodes of Ranvier in the CNS, J. Neurocytol., 13: 21–47.PubMedCrossRefGoogle Scholar
  45. Ransom, B.R., and Carlini, W.G., 1986, Electrophysiological properties of astrocytes, in: “Astrocytes”, S. Federoff and A. Vernadakis, eds., Academic Press. London.Google Scholar
  46. Ransom, B.R., and Yamate, C.C., 1984, The rat optic nerve following enucleation: a pure population of mammalian glia. Abstr. Soc. Neurosci. 10: 949.Google Scholar
  47. Recio-Pinto, E., Thornhill, W.B., Duch, D.S., Levinson, S.R., and Urban, B.W., 1990, Neuroaminidase treatment modifies the function of electroplax sodium channels in planar lipid bi-layers, Neuron 5: 675–684.PubMedCrossRefGoogle Scholar
  48. Reichenbach, A., and Eberhardt, W., 1987, Cytotopographical specialization of enzymatically isolated rabbit retinal Muller cells: K+ conductance of the cell membrane, Glia, 1:191–197. Rieger, F., Daniloff, J.K., Pincon-Raymond, M., Crossin, K.L., Grummet, M., and Edelman, G.M.Google Scholar
  49. Neuronal cell adhesion molecules and cytotactin are colocalized at the node of Ranvier, J. Cell Biol. 103: 379–391.Google Scholar
  50. Ritchie, J.M., 1991, Current perspectives in glial electrophysiology, Ann. NY Acad. Sci. 633: 331–342.PubMedCrossRefGoogle Scholar
  51. Ritchie, J.M., Black, J.A., Waxman, S.G., and Angelides, K.J., 1990, Sodium channels in the cytoplasm of Schwann cells, Proc. Natl. Acad. Sci. 87: 9290–9294.PubMedCrossRefGoogle Scholar
  52. Rosenbluth, J., 1976, Intramembranous particle distribution at the node of Ranvier and adjacent axolemma in myelinated axons of the frog brain, J. Neurocytol. 5: 731–745.PubMedCrossRefGoogle Scholar
  53. Rosenbluth, J., 1985, Intramembranous particle patches in myelin-deficient rat axons, Neurosci. Lett. 62: 19–24.PubMedCrossRefGoogle Scholar
  54. Rosenbluth, J., and Blakemore, W.F., 1984, Structural specializations in cat of chronically demyelinated spinal cord axons as seen in freeze-fracture replicas, Neurosci. Lett. 48: 171–177.PubMedCrossRefGoogle Scholar
  55. Sims, T.J., Gilmore, S.A., and Waxman, S.G., 1991, Radial glia give rise to perinodal processes, Brain Research 549: 25–35.PubMedCrossRefGoogle Scholar
  56. Sims, T.J., Waxman, S.G., Black, J.A., and Gilmore, S.A., 1985, Perinodal astrocytic processes at nodes of Ranvier in developing normal and glial cell deficient rat spinal cord, Brain Research 337: 321–333.PubMedCrossRefGoogle Scholar
  57. Smith, M.E., Somera, F.P., and Eng, L.F., 1983, Immunocytochemical for glial fibrillary acidic protein and the metabolism of cytoskeletal proteins in experimental allergic encephalomyelitis, Brain Research 264: 241–253.PubMedCrossRefGoogle Scholar
  58. Sontheimer, H., 1992, Astrocytes, as well as neurons, express a diversity of ion channels, Can. J. Physiol. Pharmacol.,in press.Google Scholar
  59. Sontheimer, H., Ransom, B.R., Cornell-Bell, A.H., Black, J.A., and Waxman, S.G., 1991a, Na+-current expression in rat hippocampal astrocytes in vitro: Alterations during development, J. Neurophysiol., 65: 3–19.PubMedGoogle Scholar
  60. Sontheimer, H., Minturn, J.D., Black, J.A., Ransom, B.R., and Waxman, S.G., 199 lb, Two types of Na+ currents in cultured rat optic nerve astrocytes: changes with time in culture and with age of culture derivation, J. Neurosci. Res. 30: 275–288.Google Scholar
  61. Sontheimer, H., Black, J.A., Ransom, B.R., and Waxman, S.G., 1992, Ion channels in spinal cord astrocytes in vitro. I. Transient expression of high levels of Na+ and K+ channels, J. Neurophysiol.,in press.Google Scholar
  62. Sontheimer, H., and Waxman, S.G., 1992, Ion channels in spinal cord astrocytes in vitro. II. Biophysical and pharmacological analysis of two Na+ current types, J. Neurophysiol.,in press.Google Scholar
  63. Srinavasan, Y., Elmer, L.W., Davis, J.Q., Bennett, V., and Angelides, KJ., 1988, Ankyrin and spectrin associate with voltage-sensitive sodium channels in brain, Nature 333: 177–179.CrossRefGoogle Scholar
  64. Stein, W.D., 1986, Transport and Diffusion across Cell Membranes, Academic Press, San Diego.Google Scholar
  65. Stys, P.K., Ransom, B.R., Waxman, S.G., and Davis, P.K., 1990, Role of extracellular calcium in anoxic injury of mammalian central white matter, Proc. Natl. Acad. Sci. 87: 4212–4216.PubMedCrossRefGoogle Scholar
  66. Trimmer, J.S., and Agnew., W.S., 1989, Molecular diversity of voltage-sensitive sodium channels, Ann. Rev. Physiol. 51: 401–418.CrossRefGoogle Scholar
  67. Waxman, S.G., 1986, The astrocyte as a component of the node of Ranvier. Trends Neurosci. 9: 250–253.CrossRefGoogle Scholar
  68. Waxman, S.G., Black, J.A., Stys, P.K., and Ransom, B.R., 1992, Ultrastructural concomitants of anoxic injury and early post-anoxic recovery in rat optic nerve, Brain Research 574: 105–119.PubMedCrossRefGoogle Scholar
  69. Waxman, S.G., and Foster, R.E., 1980, Development of the axon membrane during differentiation of myelinated fibres in spinal nerve roots, Proc. Roy. Soc. (Lond.) B 209: 441–446.CrossRefGoogle Scholar
  70. Waxman, S.G., Black, J.A., and Foster, R.E., 1982, Freeze-fracture heterogeneity of the axolemma of premyelinated fibers in the CNS, Neurology 32: 418–421.PubMedCrossRefGoogle Scholar
  71. Waxman, S.G., and Black, J.A., 1984, Freeze-fracture ultrastructure of the perinodal astrocyte and associated glial junctions, Brain Research 308: 77–87.PubMedCrossRefGoogle Scholar
  72. Waxman, S.G., and Ritchie, J.M., 1985, Organization of ion channels in the myelinated nerve fiber, Science 228: 1502–1507.PubMedCrossRefGoogle Scholar
  73. Waxman, S.G., and Quick, D.C., 1978, Infra-axonal ferric ion-ferrocyanide staining of nodes of Ranvier and initial segments in central myelinated fibers, Brain Research 144: 1–10.PubMedCrossRefGoogle Scholar
  74. Wolf, E.E., Henkart, P. and Webb, W.W., 1980, Diffusion, patching and capping of stearoylated dextrans on 3T3 cell plasma membranes, Biochemistry 19: 3893–3899.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Stephen G. Waxman
    • 1
    • 2
  1. 1.Department of NeurologyYale Medical SchoolNew HavenUSA
  2. 2.Neuroscience Research CenterV.A. HospitalWest HavenUSA

Personalised recommendations