, Volume 45, Issue 1, pp 6–12 | Cite as

Proton-Gated Ion Currents in Neurons of the Rat Spinal Ganglia and the Action of Ketanov on These Currents


We studied the desensitization kinetics of currents activated in neurons of the rat dorsal root ganglia (DRG) by short-term shifts of extracellular рН to 6.0 under conditions of primary culture using a whole-cell patch-clamp technique and intracellular perfusion. Changes of these currents under the action of ketanov were also examined. According to the decay parameters, all the observed proton-gated currents could be divided into three groups, with monoexponential fast, monoexponential slow, and biexponential desensitization kinetics. Neurons with fast monoexponential decay were divided, in turn, into two subgroups. In neurons of subgroup 1А, the decay time constant τ varied from 160 to 250 msec (n = 32), while in subgroup 1B it varied within a 250-1500 msec interval (n = 26). Neurons with the decay time constant of 1500-5000 msec formed subgroup 2A (n = 11), while cells with the longest current decay were include in subgroup 2B (t > 5000 msec, n =7). Cells of group 3, in which the currents demonstrated biexponential desensitization kinetics, had τ of the fast exponent equal to 200-600 msec (n = 21). Under conditions of application of 100 μM ketanov, the decay time constant of рН-induced currents in most DRG neurons examined decreased by 15-20%. In neurons of subgroup 2A (with decay of monoexponential currents with τ = 1500-5000 msec), currents under the action of 100 μM ketanov demonstrated not only acceleration of desensitization by 10-20%, but also a drop in the amplitude by 12‑22%.


proton-gated ion channels ASICs sensory neurons desensitization kinetics antiinflammatory anesthetics ketanov (ketorolac tromethamine) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    O. Poirot, T. Berta, J. Decosted, and S. Kellenberg, “Distinct ASIC currents are expressed in rat putative nociceptors and are modulated by nerve injury,” J. Physiol., 576, No. 1, 215–234 (2006).PubMedCrossRefGoogle Scholar
  2. 2.
    O. A. Krishtal and V. I. Pidoplichko, “A receptor for protons in the membrane of sensory neurons may participate in nociception,” Neuroscience, 6, No. 12, 2599–2601 (1981).PubMedCrossRefGoogle Scholar
  3. 3.
    O. I. Ostrovskaya, T. M. Volkova, and O. A. Krishtal, “Properties of proton-gated ion channels in sensory neurons of rats,” Neurophysiology, 35, No. 2, 82–89 (2003).CrossRefGoogle Scholar
  4. 4.
    O. Krishtal, “The ASICs: signaling molecules? Modulators?” Trends Neurosci., 26, No. 9, 477–483 (2003).PubMedCrossRefGoogle Scholar
  5. 5.
    D. Alvares de la Rosa, P. Zhang, D. Shao, et al., “Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system,” Proc. Natl. Acad. Sci. USA, 99, No. 4, 2326–2331 (2002).CrossRefGoogle Scholar
  6. 6.
    E. Lingueglia, “Acid-sensing ion channels in sensory perception,” J. Biol. Chem., 282, 17325–17329 (2007).PubMedCrossRefGoogle Scholar
  7. 7.
    T. D. Warner, F. Giuliano, I. Vojnovic, et al., “Nonsteroid drug selectivity for cyclooxygenase-1 rather than cyclooxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis,” Proc. Natl. Acad. Sci. USA, 96, 7563–7568 (1999).PubMedCrossRefGoogle Scholar
  8. 8.
    G. A. Ushakova, N. V. Kozubenko, and Y. Y. Kobeliatsky, “Ketanov prevents changes in the level of calciumbinding protein S-100-beta under postoperation pain,” Neurophysiology, 34, Nos. 2/3, 252–254 (2002).CrossRefGoogle Scholar
  9. 9.
    N. Voilley, J. Weille, J. Mamet, and M. Lazdunski, “Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors,” J. Neurosci., 21, No. 20, 8026–8033 (2001).PubMedGoogle Scholar
  10. 10.
    N. Jang, K. Ran, R. Johnson, and B. Cooper, “The proton sensitivity, Ca2+ permeability and molecular basis of ASIC channels expressed in glabrous and hairy skin afferents,” J. Neurophysiol., 95, No. 1, 2–57 (2006).Google Scholar
  11. 11.
    P. G. Kostyuk, “Intracellular perfusion of nerve cells and its effects on membrane currents,” Physiol. Rev., 64, No. 2, 435–454 (1984).PubMedGoogle Scholar
  12. 12.
    O. P. Hamill, A. Marty, E. Neher, et al., “Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches,” Pflügers Arch., 391, No. 2, 85–100 (1981).PubMedCrossRefGoogle Scholar
  13. 13.
    P. Escoubas, J. De Weille, A. Lecoq, et al., “Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels,” J. Biol. Chem., 275, 25116–25121 (2000).PubMedCrossRefGoogle Scholar
  14. 14.
    C. J. Benson, J. Xie, J. A. Wemmie, et al., “Heteromultimers of DEG/EnaC subunit form H-gated channels in mouse sensory neurons,” Proc. Natl. Acad. Sci. USA, 99, 2338–2343 (2002).PubMedCrossRefGoogle Scholar
  15. 15.
    M. Hesselager, D. Timmermann, and P. Ahring, “pH-Dependency and desensitization kinetics of heterologously expressed combinations of ASIC subunits,” J. Biol. Chem., 279, 11006–11015 (2004).PubMedCrossRefGoogle Scholar
  16. 16.
    X. Jinghui, M. P. Price, A. L. Berger, and M. J. Welsh, “DRASIC contributes to pH-gated currents in large dorsal root ganglion sensory neurons by forming heteromultimeric channels,” J. Neurophysiol., 87, 2835–2843 (2002).Google Scholar
  17. 17.
    C. Chen, S. England, A. Akopian, and J. Wood, “A sensory neuron-specific, proton-gated ion channel,” Proc. Natl. Acad. Sci. USA, 95, 10240–10245 (1998).PubMedCrossRefGoogle Scholar
  18. 18.
    E. Bassler, T. Ngo-Anh, H. Geisler, et al., “Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b,” J. Biol. Chem., 276, 33782–33787 (2001).PubMedCrossRefGoogle Scholar
  19. 19.
    K. Babinski, S. Catarsi, G. Biagini, and P. Séguéla, “Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+,” J. Biol. Chem., 275, 28519–28525 (2000).PubMedCrossRefGoogle Scholar
  20. 20.
    S. Sutherland, C. Benson, J. Adelman, and E. McCleskey, “Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons,” Proc. Natl. Acad. Sci. USA, 98, 711–716 (2001).PubMedCrossRefGoogle Scholar
  21. 21.
    J. Yagi, H. Wenk, L. Naves, and E. McCleskey, “Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia,” Circ. Res., 99, 501–509 (2006).PubMedCrossRefGoogle Scholar
  22. 22.
    R. Waldmann, F. Bassilana, J. De Weille, et al., “Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons,” J. Biol. Chem., 272, 20975–20978 (1997).PubMedCrossRefGoogle Scholar
  23. 23.
    T. Walters, M. Raizman, P. Ernest, et al., “In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac and bromfenac,” J. Cataract Refract. Surg., 33, No. 9, 1539–1545 (2007).PubMedCrossRefGoogle Scholar
  24. 24.
    D. Bustamantea and C. Paeile, “Ketorolac tromethamine: An experimental study of its analgesic effects in the rat,” Gen. J. Pharmacol., 24, No. 3, 693–698 (1993).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Bogomolets Institute of PhysiologyNational Academy of Sciences of UkraineKyivUkraine

Personalised recommendations