Cellular and Molecular Neurobiology

, Volume 14, Issue 3, pp 227–244 | Cite as

Tetrodotoxin-resistant sodium channels

  • Shigeru Yoshida


1. Tetrodotoxin (TTX) has been widely used as a chemical tool for blocking Na+ channels. However, reports are accumulating that some Na+ channels are resistant to TTX in various tissues and in different animal species. Studying the sensitivity of Na+ channels to TTX may provide us with an insight into the evolution of Na+ channels.

2. Na+ channels present in TTX-carrying animals such as pufferfish and some types of shellfish, frogs, salamanders, octopuses, etc., are resistant to TTX.

3. Denervation converts TTX-sensitive Na+ channels to TTX-resistant ones in skeletal muscle cells, i.e., reverting-back phenomenon. Also, undifferentiated skeletal muscle cells contain TTX-resistant Na+ channels. Cardiac muscle cells and some types of smooth muscle cells are considerably insensitive to TTX.

4. TTX-resistant Na+ channels have been found in cell bodies of many peripheral nervous system (PNS) neurons in both immature and mature animals. However, TTX-resistant Na+ channels have been reported in only a few types of central nervous system (CNS). Axons of PNS and CNS neurons are sensitive to TTX. However, some glial cells have TTX-resistant Na+ channels.

5. Properties of TTX-sensitive and TTX-resistant Na+ channels are different. Like Ca2+ channels, TTX-resistant Na+ channels can be blocked by inorganic (Co2+, Mn2+, Ni2+, Cd2+, Zn2+, La3+) and organic (D-600) Ca2+ channel blockers. Usually, TTX-resistant Na+ channels show smaller single-channel conductance, slower kinetics, and a more positive current-voltage relation than TTX-sensitive ones.

6. Molecular aspects of the TTX-resistant Na+ channel have been described. The structure of the channel has been revealed, and changing its amino acid(s) alters the sensitivity of the Na+ channel to TTX.

7. TTX-sensitive Na+ channels seem to be used preferentially in differentiated cells and in higher animals instead of TTX-resistant Na+ channels for rapid and effective processing of information.

8. Possible evolution courses for Na+ and Ca2+ channels are discussed with regard to ontogenesis and phylogenesis.

Key words

tetrodotoxin Na+ channels neurons muscles development 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aguayo, L. G., Weight, F. F., and White, G. (1991). TTX-sensitive action potentials and excitability of adult rat sensory neurons cultured in serum- and exogenous nerve growth factor-free medium.Neurosci. Lett. 121:88–92.PubMedGoogle Scholar
  2. Akaike, N., and Takahashi, K. (1992). Tetrodotoxin-sensitive calcium-conducting channels in the rat hippocampal CA1 region.J Physiol. (Lond.) 450:529–546.Google Scholar
  3. Armstrong, C. M., and Bezanilla, F. (1974). Charge movement associated with the opening and closing of the activation gates of Na channels.J. Gen. Physiol. 63:533–552.PubMedGoogle Scholar
  4. Baccaglini, P., and Cooper, E. (1982). Electrophysiological studies of new-born rat nodose neurones in cell culture.J. Physiol. (Lond.) 324:429–439.Google Scholar
  5. Barchi, R. L. (1988). Probing the molecular structure of the voltage-dependent sodium channel.Annu. Rev. Neurosci. 11:455–495.PubMedGoogle Scholar
  6. Barres, B. A., Chun, L. L. Y., and Corey, D. P. (1989). Glial and neuronal forms of the voltage-dependent sodium channel: Characteristics and cell-type distribution.Neuron 2:1375–1388.PubMedGoogle Scholar
  7. Barres, B. A., Chun, L. L. Y., and Corey, D. P. (1990). Ion channels in vertebrate glia.Annu. Rev. Neurosci. 13:441–474.PubMedGoogle Scholar
  8. Benoit, E., Corbier, A., and Dubois, J. M. (1985). Evidence for two transient sodium currents in the frog node of Ranvier.J. Physiol. (Lond.) 361:339–360.Google Scholar
  9. Bevan, S., Chiu, S. Y., Gray, P. T. A., and Ritchie, J. M. (1985). The presence of voltage-gated sodium, potassium and chloride channels in rat cultured astrocytes.Proc. R. Soc. London Ser. B 225:299–313.Google Scholar
  10. Bkaily, G., Jacques, D., Sculptoreanu, A., Yamamoto, T., Carrier, D., Vigneault, D., and Sperelakis, N. (1991). Apamin, a highly potent blocker of the TTX- and Mn2+-insensitive fast transient Na+ current in young embryonic heart.J. Mol. Cell. Cardiol. 23:25–39.PubMedGoogle Scholar
  11. Bossu, J. L., and Feltz, A. (1984). Patch-clamp study of the tetrodotoxin-resistant sodium current in group C sensory neurons.Neurosci. Lett. 51:241–246.PubMedGoogle Scholar
  12. Brown, A. M., Lee, K. S., and Powell, T. (1981). Sodium current in single rat heart muscle cells.J. Physiol. (Lond.) 318:479–500.Google Scholar
  13. Caffrey, J. M., Eng, D. L., Black, J. A., Waxman, S. G., and Kocsis, J. D. (1992). Three types of sodium channels in adult rat dorsal root ganglion neurons.Brain Res. 592:283–297.PubMedGoogle Scholar
  14. Campbell, D. T. (1992). Large and small vertebrate sensory neurons express different Na and K channel subtypes.Proc. Natl. Acad. Sci. USA 89:9569–9573.PubMedGoogle Scholar
  15. Campbell, D. T. (1993). Single-channel current/voltage relationships of two kinds of Na+ channel in vertebrate sensory neurons.Pflügers Arch. 423:492–496.Google Scholar
  16. Catterall, W. A. (1980). Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes.Annu. Rev. Pharmacol. Toxicol. 20:15–43.PubMedGoogle Scholar
  17. Catterall, W. A. (1988). Structure and function of voltage-sensitive ion channels.Science 242:50–61.PubMedGoogle Scholar
  18. Chiu, S. Y. (1987). Sodium currents in axon-associated Schwann cells from adult rabbits.J. Physiol. (Lond.) 386:181–203.Google Scholar
  19. Clark, R. B., Tse, A., and Giles, W. R. (1990). Electrophysiology of parasympathetic neurones isolated from the interatrial septum of bull-frog heart.J. Physiol. (Lond.) 427:89–125.Google Scholar
  20. Cook, J. (1777).A Voyage Towards the South Pole and Around the World, Vol. 2, Straham and Cadell, London, pp. 112–113.Google Scholar
  21. Dichter, M. A., and Fischbach, G. D. (1977). The action potential of chick dorsal root ganglion neurones maintained in cell culture.J. Physiol. (Lond.) 267:281–298.Google Scholar
  22. Elliott, A. A., and Elliott, J. R. (1993). Characterization of TTX-sensitive and TTX-resistant sodium currents in small cells from adult rat dorsal root ganglia.J. Physiol. (Lond.) 463:39–56.Google Scholar
  23. Fedulova, S. A., Kostyuk, P. G., and Veslovsky, N. S. (1991). Ionic mechanisms of electrical excitability in rat sensory neurons during postnatal ontogenesis.Neuroscience 41:303–309.PubMedGoogle Scholar
  24. Flamm, R. E., Birnberg, N. C., and Kaczmarek, L. K. (1990). Transfection of activated ras into an excitable cell line (AtT-20) alters tetrodotoxin sensitivity of voltage-dependent sodium current.Pflügers Arch. 416:120–125.Google Scholar
  25. Fukuda, J., and Kameyama, M. (1980). Tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in tissue-cultured spinal ganglion neurons from adult mammals.Brain Res. 182:191–197.PubMedGoogle Scholar
  26. Gallego, R. (1983). The ionic basis of action potentials in petrosal ganglion cells of the cat.J. Physiol. (Lond.) 342:591–602.Google Scholar
  27. Gonoi, T., Sherman, S. J., and Catterall, W. A. (1985). Voltage clamp analysis of tetrodotoxin-sensitive and -insensitive sodium channels in rat muscle cells developing in vitro.J. Neurosci. 5:2559–2564.PubMedGoogle Scholar
  28. Hagiwara, S., and Takahashi, K. (1967). Resting and spike potentials of skeletal muscle fibres of salt-water elasmobranch and teleost fish.J. Physiol. (Lond.) 190:499–518.Google Scholar
  29. Halstead, B. W. (1967).Poisonous and Venomous Marine Animals of the World, U.S. Government Printing Office, Washington, DC, VolI, pp. 83–87, Vol. II, pp. 679–844.Google Scholar
  30. Harper, A. A., and Lawson, S. N. (1985a). Conduction velocity is related to morphological cell type in rat dorsal root ganglion neurones.J. Physiol. (Lond.) 359:31–46.Google Scholar
  31. Harper, A. A., and Lawson, S. N. (1985b). Electrical properties of rat dorsal root ganglion neurones with different peripheral nerve conduction velocities.J. Physiol. (Lond.) 359:47–63.Google Scholar
  32. Harris, J. B., and Thesleff, S. (1971). Studies on tetrodotoxin resistant action potentials in denervated skeletal muscle.Acta Physiol. Scand. 83:382–388.PubMedGoogle Scholar
  33. Heinemann, S. H., Terlau, H., Stühmer, W., Imoto, K., and Numa, S. (1992). Calcium channel characteristics conferred on the sodium channel by single mutations.Nature 356:441–443.PubMedGoogle Scholar
  34. Heyer, E. J., and MacDonald, R. L. (1982). Calcium- and sodium-dependent action potentials of mouse spinal cord and dorsal root ganglion neurons in cell culture.J. Neurophysiol. 47:641–655.PubMedGoogle Scholar
  35. Hille, B. (1992).Ionic Channels of Excitable Membranes, Sinauer Associates, Sunderland, MA.Google Scholar
  36. Ikeda, S. R., and Schofield, G. G. (1987). Tetrodotoxin-resistant sodium current of rat nodose neurones: monovalent cation selectivity and divalent cation block.J. Physiol. (Lond.) 389:255–270.Google Scholar
  37. Ikeda, S. R., Schofield, G. G., and Weight, F. F. (1986). Na+ and Ca2+ currents of acutely isolated adult rat nodose ganglion cells.J. Neurophysiol. 55:527–539.PubMedGoogle Scholar
  38. Jones, S. W. (1987). Sodium currents in dissociated bull-frog sympathetic neurones.J. Physiol. (Lond.) 389:605–627.Google Scholar
  39. Kallen, R. G., Sheng, Z. H., Yang, J., Chen, L. Q., Rogart, R. B., and Barchi, R. L. (1990). Primary structure and expression of a sodium channel characteristic of denervated and immature rat skeletal muscle.Neuron 4:233–242.PubMedGoogle Scholar
  40. Kano, M. (1975). Development of excitability in embryonic chick skeletal muscle cells.J. Cell. Physiol. 86:503–510.PubMedGoogle Scholar
  41. Kao, C. Y. (1966). Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena.Pharmacol. Rev. 18:997–1049.PubMedGoogle Scholar
  42. Kao, C. Y., and Fuhrman, F. A. (1963). Pharmacological studies on tarichatoxin, a potent neurotoxin.J. Pharmacol. Exp. Ther. 140:31–40.Google Scholar
  43. Kao, C. Y., and Levinson, S. R. (Eds.) (1986).Tetrodotoxin, Saxitoxin, and the Molecular Biology of the Sodium Channel, Ann. N.Y. Acad. Sci. Vol. 479.Google Scholar
  44. Kidokoro, Y. (1973). Development of action potentials in a clonal rat skeletal muscle cell line.Nature 241:158–159.Google Scholar
  45. Kidokoro, Y. (1975). Sodium and calcium components of the action potential in a developing skeletal muscle cell line.J. Physiol. (Lond.) 244:145–159.Google Scholar
  46. Kidokoro, Y., Grinnell, A. D., and Eaton, D. C. (1974). Tetrodotoxin sensitivity of muscle action potentials in pufferfishes and related fishes.J. Comp. Physiol. 89:59–72.Google Scholar
  47. Kleinhaus, A. L., and Prichard, J. W. (1976). Sodium dependent tetrodotoxin-resistant action potentials in a leech neuron.Brain Res. 102:368–373.PubMedGoogle Scholar
  48. Kostyuk, P. G., Veselovsky, N. S., and Tsyndrenko, A. Y. (1981). Ionic currents in the somatic membrane of rat dorsal root ganglion neurons. I. Sodium currents.Neuroscience 6:2423–2430.PubMedGoogle Scholar
  49. Kostyuk, P. G., Pronchuk, N., Savchenko, A., and Verkhratsky, A. (1993). Calcium currents in aged rat dorsal root ganglion neurones.J. Physiol. (Lond.) 461:467–483.Google Scholar
  50. Lawson, S. N., Harper, A. A., Harper, E. I., Garson, J. A., and Anderton, B. H. (1984). A monoclonal antibody against neurofilament protein specifically labels a subpopulation of rat sensory neurones.J. Comp. Neurol. 228:263–272.PubMedGoogle Scholar
  51. Mandel, G. (1992). Tissue-specific expression of the voltage-sensitive sodium channel.J. Membr. Biol. 125:193–205.PubMedGoogle Scholar
  52. McDonald, T. F., Sachs, H. G., and DeHaan, R. L. (1973). Tetrodotoxin desensitization in aggregates of embryonic chick heart cells.J. Gen. Physiol. 62:286–302.PubMedGoogle Scholar
  53. McLean, M. J., Bennett, P. B., and Thomas, R. M. (1988). Subtypes of dorsal root ganglion neurons based on different inward currents as measured by whole-cell voltage clamp.Mol. Cell. Biochem. 80:95–107.PubMedGoogle Scholar
  54. Matsuda, Y., Yoshida, S., and Yonezawa, T. (1976). A Ca-dependent regenerative response in rodent dorsal root ganglion cellsin vitro.Brain Res. 115:334–338.PubMedGoogle Scholar
  55. Matsuda, Y., Yoshida, S., and Yonezawa, T. (1978). Tetrodotoxin sensitivity and Ca component of action potentials of mouse dorsal root ganglion cells culturedin vitro.Brain Res. 154:69–82.PubMedGoogle Scholar
  56. Mercuri, N. B., Stratta, F., Calabresi, P., and Bernardi, G. (1993). Neurotensin induces an inward current in rat mesencephalic dopaminergic neurons.Neurosci. Lett. 153:192–196.PubMedGoogle Scholar
  57. Mitani, S. (1985). The reduction of calcium current associated with early differentiation of the murine embryo.J. Physiol. (Lond.) 363:71–86.Google Scholar
  58. Miyazaki, S., Takahashi, K., and Tsuda, J. (1974). Electrical excitability in the egg cell membrane of the tunicate.J. Physiol. (Lond.) 238:37–54.Google Scholar
  59. Miyazaki, S., Ohmori, H., and Sasaki, S. (1975). Action potential and non-linear current-voltage relation in starfish oocytes.J. Physiol. (Lond.) 246:37–54.Google Scholar
  60. Miyazawa, K., Jeon, J. K., Noguchi, T., Ito, K., and Hashimoto, K. (1987). Distribution of tetrodotoxin in the tissues of the flatwormPlanocera multitentaculata (Platyhelminthes).Toxicon 25:975–980.PubMedGoogle Scholar
  61. Morita, K., and Katayama, Y. (1989). Bullfrog dorsal root ganglion cells having tetrodotoxin-resistant spikes are endowed with nicotinic receptors.J. Neurophysiol. 62:657–664.PubMedGoogle Scholar
  62. Mosher, H. S. (1986). The chemistry of tetrodotoxin.Ann. N.Y. Acad. Sci. 479:32–43.PubMedGoogle Scholar
  63. Mosher, H. S., and Fuhrman, F. A. (1984). Occurrence and origin of tetrodotoxin. InSeafood Toxins, (E. P. Ragelis, Ed.), American Chemical Society Symposium 262, pp. 333–344.Google Scholar
  64. Mosher, H. S., Fuhrman, F. A., Buchwald, H. D., and Fischer, H. G. (1964). Tarichatoxin-tetrodotoxin: A potent neurotoxin.Science 144:1100–1114.PubMedGoogle Scholar
  65. Muraki, K., Imaizumi, Y., and Watanabe, M. (1991). Sodium currents in smooth muscle cells freshly isolated from stomach fundus of the rat and ureter of the guinea-pig.J. Physiol. (Lond.) 442:351–375.Google Scholar
  66. Narahashi, T. (1974). Chemicals as tools in the study of excitable membrane.Physiol. Rev. 54:813–889.PubMedGoogle Scholar
  67. Narahashi, T., Moore, J. W., and Scott, W. R. (1964). Tetrodotoxin blockage of sodium conductance increase in lobster giant axons.J. Gen. Physiol. 47:965–974.PubMedGoogle Scholar
  68. Neumcke, B. (1990). Diversity of sodium channels in adult and cultured cells, in oocytes and in lipid bilayers.Rev. Physiol. Biochem. Pharmacol. 115:1–49.PubMedGoogle Scholar
  69. Noda, M., Shimizu, S., Tanabe, T., Takai, T., Kayano, T., Ikeda, T., Takahashi, H., Nakayama, H., Kanaoka, Y., Minamino, N., Kanagawa, K., Matsuo, H., Raftery, M. A., Hirose, T., Inayama, S., Hayashida, H., Miyata, T., and Numa, S. (1984). Primary structure ofElectrophorus electricus sodium channel deduced from cDNA sequence.Nature 312:121–127.PubMedGoogle Scholar
  70. Noda, M., Ikeda, T., Kayano, T., Suzuki, H., Takeshima, H., Kurasaki, M., Takahashi, H., and Numa, S. (1986). Existence of distinct sodium channel messenger RNAs in rat brain.Nature 320:188–192.PubMedGoogle Scholar
  71. Noda, M., Suzuki, H., Numa, S., and Stühmer, W. (1989). A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II.FEBS Lett. 259:213–216.PubMedGoogle Scholar
  72. Noguchi, T., Jeon, J. K., Arakawa, O., Sugita, H., Deguchi, Y., Shida, Y., and Hashimoto, K. (1986). Occurrence of tetrodotoxin and anhydrotetrodotoxin inVibrio sp. isolated from the intestines of a xanthid crab,Atergatis floridus.J. Biochem. 99:311–314.PubMedGoogle Scholar
  73. Numa, S. (1989). A molecular view of neurotransmitter receptors and ionic channels.Harvey Lect. 83:121–165.Google Scholar
  74. Ogata, N., and Tatebayashi, H. (1992a). Ontogenic development of the TTX-sensitive and TTX-insensitive Na+ channels in neurons of the rat dorsal root ganglia.Dev. Brain Res. 65:93–100.Google Scholar
  75. Ogata, N., and Tatebayashi, H. (1992b). Slow inactivation of tetrodotoxin-insensitive Na+ channels in neurons of rat dorsal root ganglia.J. Membr. Biol. 129:71–80.PubMedGoogle Scholar
  76. Ogata, N., and Tatebayashi, H. (1992c) Na+ current kinetics are not the determinants of the action potential duration in neurons of the rat ventral tegmental area.Brain Res. Bull. 29:691–695.PubMedGoogle Scholar
  77. Ogata, N., and Tatebayashi, H. (1993). Kinetic analysis of two types of Na+ channels in rat dorsal root ganglia.J. Physiol. (Lond.) 466:9–37.Google Scholar
  78. Okamoto, H., Takahashi, K., and Yoshii, M. (1976). Membrane currents of the tunicate egg under the voltage-clamp condition.J. Physiol. (Lond.) 254:607–638.Google Scholar
  79. Okamoto, H., Takahashi, K., and Yamashita, N. (1977). Ionic currents through the membrane of the mammalian oocytes and their comparison with those in the tunicate and sea urchin.J. Physiol. (Lond.) 267:465–495.Google Scholar
  80. Okamura, Y., and Shidara, M. (1990). Changes in sodium channels during neural differentiation in the isolated blastomere of the ascidian embryo.J. Physiol. (Lond.) 431:39–74.Google Scholar
  81. Omri, G., and Meiri, H. (1990). Characterization of sodium currents in mammalian sensory neurons cultured in serum-free defined medium with and without nerve growth factor.J. Membr. Biol. 115:13–29.PubMedGoogle Scholar
  82. Pappone, P. A. (1980). Voltage-clamp experiments in normal and denervated mammalian skeletal muscle fibres.J. Physiol. (Lond.) 306:377–410.Google Scholar
  83. Petersen, M., Pierau, Fr. K., and Weyrich, M. (1987). The influence of capsaicin on membrane currents in dorsal root ganglion neurones of guinea-pig and chicken.Pflügers Arch. 409:403–410.Google Scholar
  84. Prince, R. C. (1988). Tetrodotoxin.Trends Biochem. Sci. 13:76–77.PubMedGoogle Scholar
  85. Raggenbass, M., and Dreifuss, J. J. (1992). Mechanism of action of oxytocin in rat vagal neurones: induction of a sustained sodium-dependent current.J. Physiol. (Lond.) 457:131–142.Google Scholar
  86. Ransom, B. R., and Holz, R. W. (1977). Ionic determinants of excitability in cultured mouse dorsal root ganglion and spinal cord cells.Brain Res. 136:445–453.PubMedGoogle Scholar
  87. Redfern, P., and Thesleff, S. (1971). Action potential generation in denervated rat skeltal muscle. II. Action of tetrodotoxin.Acta Physiol. Scand. 82:70–79.PubMedGoogle Scholar
  88. Ritchie, J. M., and Rogart, R. B. (1977). The binding of saxitoxin and tetrodotoxin to excitable tissue.Rev. Physiol. Biochem. Pharmacol. 79:1–50.PubMedGoogle Scholar
  89. Roy, M. L., and Narahashi, T. (1992). Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons.J. Neurosci. 12:2104–2111.PubMedGoogle Scholar
  90. Russel, F. E. (1965). Marine toxins and venomous and poisonous marine animals.Adv. Marine Biol. 3:255–383.Google Scholar
  91. Satin, J., Kyle, J. W., Chen, M., Bell, P., Cribbs, L. L., Fozzard, H. A., and Rogart, R. B. (1992). A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties.Science 256:1202–1205.PubMedGoogle Scholar
  92. Schlichter, L. C. (1983). A role for action potentials in maturingRana pipiens oocytes.Dev. Biol. 98:60–69.PubMedGoogle Scholar
  93. Schlichter, L. C., Bader, C. R., and Bernheim, L. (1991). Development of anomalous rectification (l h) and of a tetrodotoxin-resistant sodium current in embryonic quail neurones.J. Physiol. (Lond.) 442:127–145.Google Scholar
  94. Schofield, G. G., and Ikeda, S. R. (1988). Sodium and calcium currents of acutely isolated adult rat superior cervical ganglion neurons.Pflügers Arch. 411:481–490.Google Scholar
  95. Schwartz, A., Palti, Y., and Meiri, H. (1990). Structural and developmental differences between three types of Na channels in dorsal root ganglion cells of newborn rats.J. Membr. Biol. 116:117–128.PubMedGoogle Scholar
  96. Shigenobu, K., and Sperelakis, N. (1971). Development of sensitivity to tetrodotoxin of chick embryonic hearts with age.J. Mol. Cell. Cardiol. 3:271–286.PubMedGoogle Scholar
  97. Shrager, P., Chiu, S. Y., and Ritchie, J. M. (1985). Voltage-dependent sodium and potassium channels in mammalian cultured Schwann cells.Proc. Natl. Acad. Sci. USA 82:948–952.PubMedGoogle Scholar
  98. Sigworth, F. J., and Spalding, B. C. (1980). Chemical modification reduces the conductance of sodium channels in nerve.Nature 283:293–295.PubMedGoogle Scholar
  99. Spalding, B. C. (1980). Properties of toxin-resistant sodium channels produced by chemical modification in frog skeletal muscle.J. Physiol. (Lond.) 305:485–500.Google Scholar
  100. Sperelakis, N., and Shigenobu, K. (1972). Changes in membrane properties of chick embryonic hearts during development.J. Gen. Physiol. 60: 430–453.PubMedGoogle Scholar
  101. Spitzer, N. C. (1979). Ion channels in development.Annu. Rev. Neurosci. 2:363–397.PubMedGoogle Scholar
  102. Stansfeld, C. E., and Wallis, D. I. (1985). Properties of visceral primary afferent neurons in the nodose ganglion of the rabbit.J. Neurophysiol. 54:245–260.PubMedGoogle Scholar
  103. Sutton, F., Davidson, N., and Lester, H. (1988). Tetrodotoxin-sensitive voltage-dependent Na currents recorded fromXenopus oocytes injected with mammalian cardiac muscle RNA.Mol. Brain Res. 3:195–200.Google Scholar
  104. Takahashi, K., Kameda, H., Kataoka, M., Ueno, S., and Akaike, N. (1992). Effects of Ca2+ antagonists and antiepileptics on tetrodotoxin-sensitive Ca2+-conducting channels in isolated rat hippocampal CA1 neurons.Neurosci. Lett. 148:60–62.PubMedGoogle Scholar
  105. Terlau, H., Heinemann, S. H., Stühmer, W., Pusch, M., Conti, F., Imoto, K., and Numa, S. (1991). Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II.FEBS Lett. 293:93–96.PubMedGoogle Scholar
  106. Thio, C. L., and Sontheimer, H. (1993). Differential modulation of TTX-sensitive and TTX-resistant Na+ channels in spinal cord astrocytes following activation of protein kinase C.J. Neurosci. 13:4889–4897.PubMedGoogle Scholar
  107. Trimmer, J. S., and Agnew, W. S. (1989). Molecular diversity of voltage-sensitive Na channels.Annu. Rev. Physiol. 51:401–418.PubMedGoogle Scholar
  108. Trimmer, J. S., Cooperman, S. S., Agnew, W. S., and Mandel, G. (1990). Regulation of muscle sodium channel transcripts during development and in response to denervation.Dev. Biol. 142:360–367.PubMedGoogle Scholar
  109. Twarog, B. M., Hidaka, T., and Yamaguchi, H. (1972). Resistance to tetrodotoxin and saxitoxin in nerves of bivalve molluscs.Toxicon 10:273–278.PubMedGoogle Scholar
  110. Ulbricht, W. (1981). Kinetics of drug action and equilibrium results at the node of Ranvier.Physiol. Rev. 61:785–828.PubMedGoogle Scholar
  111. Unsworth, B. R., and Hafemann, D. R. (1975). Tetrodotoxin binding as a marker for functional differentiation of various brain regions during chick and mouse development.J. Neurochem. 24:261–270.PubMedGoogle Scholar
  112. Wald, F. (1972). Ionic differences between somatic and axonal action potentials in snail giant neurones.J. Physiol. (Lond.) 220:267–281.Google Scholar
  113. Weiss, R. E., and Horn, R. (1986). Functional differences between two classes of sodium channels in developing rat skeletal muscle.Science 233:361–364.PubMedGoogle Scholar
  114. Weiss, R. E., and Sidell, N. (1991). Sodium currents during differentiation in a human neuroblastoma cell line.J. Gen. Physiol. 97:521–539.PubMedGoogle Scholar
  115. White, J. A., Alonso, A., and Kay, A. R. (1993). A heart-like Na+ current in the medial entorhinal cortex.Neuron 11:1037–1047.PubMedGoogle Scholar
  116. White, M. M., Chen, L. Q., Kleinfield, R., Kallen, R. G., and Barchi, R. L. (1991). SkM2, a Na+ channel cDNA clone from denervated skeletal muscle, encodes a tetrodotoxin-insensitive Na+ channel.Mol. Pharmacol. 39:604–608.PubMedGoogle Scholar
  117. Yamaguchi, K. (1992). Electrophysiological properties of the growth cone membrane of the cultured rat dorsal root ganglion neuron.Jpn. J. Physiol. 42(Suppl).:S119 (abstr.).Google Scholar
  118. Yang, J. S., Sladky, J. T., Kallen, R. G., and Barchi, R. L. (1991). TTX-sensitive and TTX-insensitive sodium channel mRNA transcripts are independently regulated in adult skeletal muscle after denervation.Neuron 7:421–427.PubMedGoogle Scholar
  119. Yasumoto, T., Yasumura, D., Yotsu, M., Michishita, T., Endo, A., and Kotani, Y. (1986). Bacterial production of tetrodotoxin and anhydrotetrodotoxin.Agr. Biol. Chem. 50:793–795.Google Scholar
  120. Yoshida, S. (1982). Na and Ca spikes produced by ions passing through Ca channels in mouse ovarian oocytes.Pflügers Arch. 395:84–86.Google Scholar
  121. Yoshida, S. (1983a). Permeation of divalent and monovalent cations through the ovarian oocyte membrane of the mouse.J. Physiol. (Lond.) 339:631–642.Google Scholar
  122. Yoshida, S. (1983b). Excitability of ovarian oocytes and cleaving embryos of the mouse. InPhysiology of Excitable Cells (A. D. Grinnell and W. J. Moody Eds.), Alan R. Liss, New York, pp. 267–277.Google Scholar
  123. Yoshida, S. (1985). Action potentials dependent on monovalent cations in developing mouse embryos.Dev. Biol. 110:200–206.PubMedGoogle Scholar
  124. Yoshida, S. (1986a). Effects of the calcium channel blocker diltiazem on the excitability of mouse oocytes.Gamete Res. 13:309–316.Google Scholar
  125. Yoshida, S. (1986b). Electrical properties of oocytes and developing embryos of the mouse. InMembrane Excitation and Macromolecules (A. Watanabe, S., Terakawa, and K. Uchizono, Eds.), Biomedical Research Foundation, Tokyo, pp. 99–102.Google Scholar
  126. Yoshida, S., and Matsuda, Y. (1979). Studies on sensory neurons of the mouse with intracellular-recording and horseradish peroxidase-injection techniques.J. Neurophysiol. 42:1134–1145.PubMedGoogle Scholar
  127. Yoshida, S., and Matsuda, Y. (1980). Responses dependent on alkaline earth cations (Ca, Sr, Ba) in dorsal root ganglion cells of the adult mouse.Brain Res. 188:593–597.PubMedGoogle Scholar
  128. Yoshida, S., Matsuda, Y., and Samejima, A. (1978). Tetrodotoxin-resistant sodium and calcium components of action potentials in dorsal root ganglion cells of the adult mouse.J. Neurophysiol. 41:1096–1106.PubMedGoogle Scholar
  129. Yoshida, S., Mukainaka, T., and Yonezawa, T. (1979). Effects of alkaline earth cations (Ca, Sr, Ba) on cultured spinal neurons of the mouse. A light and electron microscopic study.Brian Res. 173:168–173.Google Scholar
  130. Yoshida, S., Matsuda, Y., and Sasaki, K. (1980a). Calcium and tetrodotoxin-resistant sodium currents in mammalian neurons. InTopics in General Physiology and Biophysics The Committee for Publication in Honor of Professor A. Inouye (Ed.), Kitami Shobo, Tokyo, pp. 92–102.Google Scholar
  131. Yoshida, S., Matsuda, Y., and Yonezawa, T. (1980b). Spontaneous discharges caused by increasing external Na ion or divalent cation concentration in the mouse dorsal root ganglion cells in culture.Brain Res. 196:560–564.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Shigeru Yoshida
    • 1
  1. 1.Department of PhysiologyFukui Medical SchoolFukuiJapan

Personalised recommendations