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Ionic Currents and Endogenous Rhythm Generation in the pre-Bötzinger Complex: Modelling and In Vitro Studies

  • Ilya A. Rybak
  • Natalia A. Shevtsova
  • Walter M. St. John
  • Julian F. R. Paton
  • Olivier Pierrefiche
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 551)

Abstract

The pre-Bötzinger complex (pBC), a small area in the rostroventrolateral medulla, has been suggested to represent a “kernel” of the mammalian respiratory network1, 2, 3, 4, 5. The in vitro preparations from neonatal rodents containing this area can, under certain experimental conditions, generate an intrinsic rhythmic activity4,5. This activity does not require inhibitory neurotransmission6 and, therefore, is likely to be generated by a population of pacemaker neurons in the pBC1, 2, 3, 4, 5. At the same time, the “decrementing” discharge pattern of rhythmic activity in the pBC recorded in vitro differs from the pattern of respiratory discharges observed under normal conditions in vivo (“eupnoea”) and is similar to gasping pattern7, 8. In order to establish possible relationships of the intrinsic rhythmic activity in the pBC to the respiratory rhythmogenesis in vivo, it is important to analyse the conditions in which this activity occurs in vitro and to compare these conditions with the rhythmogenic conditions during eupnoea and gasping in vivo. According to the preliminary modelling studies9, the in vitro rhythmic activity in the pBC may be dependent on a relative expression of the voltage-gated potassium and persistent sodium currents in pBC neurons. Here we present the results of our combined modelling and in vitro studies performed to test this modelling prediction. Our studies focused on the involvement of the potassium and persistent sodium currents in the endogenous rhythmic activity in the pBC in vitro and on the possible relation of this activity to the genesis of the respiratory oscillations in vivo.

Keywords

Rhythmic Activity Burst Activity Persistent Sodium Current Respiratory Rhythm Generation External Potassium Concentration 
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.

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References

  1. 1.
    J. C. Smith, R. J. Butera, N. Koshiya, C. Del Negro, C. G. Wilson, and S. M. Johnson. Respiratory rhythm generation in neonatal and adult mammals: The hybrid pacemaker-network model. Respir. Physiol. 122, 131–147 (2000).CrossRefPubMedGoogle Scholar
  2. 2.
    R. J. Butera, J. R. Rinzel, and J. C. Smith, Models of respiratory rhythm generation in the pre-Bötzinger complex: I. Bursting pacemaker neurons, J. Neurophysiol. 82, 382–397 (1999).PubMedGoogle Scholar
  3. 3.
    R. J. Butera, J. R. Rinzel, and J. C. Smith, Models of respiratory rhythm generation in the pre-Bötzinger complex: II. Populations of Coupled Pacemaker Neurons. J. Neurophysiol. 82, 398–415 (1999).PubMedGoogle Scholar
  4. 4.
    S. M. Johnson, J. C. Smith, G. D. Funk, and J. L. Feldman, Pacemaker behavior of respiratory neurons in medullary slices from neonatal rat. J. Neurophysiol. 72, 2598–2608 (1994).PubMedGoogle Scholar
  5. 5.
    N. Koshiya and J. C. Smith, Neuronal pacemaker for breathing visualized in vitro. Nature 400(6742), 360–363 (1999).CrossRefPubMedGoogle Scholar
  6. 6.
    X. M. Shao and J. L. Feldman, Respiratory rhythm generation and synaptic inhibition of expiratory neurons in pre-Bötzinger complex: differential roles of glycinergic and gabaergic neural transmission, J. Neurophysiol. 77, 1853–1860 (1997).PubMedGoogle Scholar
  7. 7.
    W. M. St.-John, Medullary regions for neurogenesis of gasping: noeud vital or noeuds vitals? J. Appl. Physiol. 81, 1865–1877 (1996).PubMedGoogle Scholar
  8. 8.
    W. M. St.-John, Neurogenesis of patterns of automatic ventilatory activity. Prog. Neurobiol. 56, 97–117 (1998).CrossRefPubMedGoogle Scholar
  9. 9.
    I. A. Rybak, J. F. R. Paton, R. F. Rogers, and W. M. St.-John, Generation of the respiratory rhythm: state dependency and switching. Neurocomputing 44–46, 605–614 (2002).CrossRefGoogle Scholar
  10. 10.
    I. A. Rybak, K. Ptak, N. A. Shevtsova, and D. R. McCrimmon, D R. Sodium currents in neurons from the rostroventrolateral medulla of the rat, J Neurophysiol. 90, 1635–1642 (2003).CrossRefPubMedGoogle Scholar
  11. 11.
    I. A. Rybak, N. A. Shevtsova, W. M. St.-John, J. F. R. Paton, and O. Pierrefiche, Endogenous rhythm generation in the pre-Bötzinger complex and ionic currents: Modelling and in vitro studies. Eur. J. Neurosci. 18, 239–257 (2003).CrossRefPubMedGoogle Scholar
  12. 12.
    W. M. St.-John, and J. F. R. Paton, Neurogenesis of gasping does not require inhibitory transmission using GABAA or glycine receptors. Respir. Physiol. Neurobiol., 132, 265–277 (2002).CrossRefPubMedGoogle Scholar
  13. 13.
    W. M. St.-John, I. A. Rybak, and J. F. R., Paton, Potential switch from eupnea to fictive gasping after blockade of glycine transmission and potassium channels, Am. J. Physiol. (Integr. Comp. Physiol.) 283, R721–R731 (2002).Google Scholar
  14. 14.
    C. Jiang and G. G. Haddad, A direct mechanism for sensing low oxygen levels by central neurons. Proc. Natl. Acad. Sci. USA, 91, 7198–7201 (1994).CrossRefPubMedGoogle Scholar
  15. 15.
    L. Conforti, L. and D. E. Millhorn, Selective inhibition of a slow-inactivating voltage-dependent K+ channels in rat PC12 cells by hypoxia, J. Physiol. Land., 502, 293–305 (1997).CrossRefGoogle Scholar
  16. 16.
    Gebhardt, C. and U. Heinemann, Anoxic decrease in potassium outward currents of hippocampal cultured neurons in absence and presence of dithionite. Brain Res. 837, 270–276 (1999).CrossRefGoogle Scholar
  17. 17.
    A. K. Hammarström and P. W. Gage, Inhibition of oxidative metabolism increases persistent sodium current in rat CA1 hippocampal neurons, J. Physiol. 510, 735–741 (1998).CrossRefPubMedGoogle Scholar
  18. 18.
    E. M. Horn and T. G. Waldrop, Hypoxic augmentation of fast-inactivating and persistent sodium currents in rat caudal hypothalamic neurons. J. Neurophysiol., 84, 2572–2581 (2000).PubMedGoogle Scholar
  19. 19.
    J. E. Melton, S. C. Kadia, Q. P. Yu, J. A. Neubauer, and N. H. Edelman, Respiratory and sympathetic activity during recovery from hypoxic depression and gasping in cats, J. Appl. Physiol. 80, 1940–1948 (1996).CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic/Plenum Publishers, New York 2004

Authors and Affiliations

  • Ilya A. Rybak
    • 1
  • Natalia A. Shevtsova
    • 1
  • Walter M. St. John
    • 2
  • Julian F. R. Paton
    • 3
  • Olivier Pierrefiche
    • 4
  1. 1.School of Biomedical Engineering, Science and Health SystemsDrexel UniversityPhiladelphia
  2. 2.Department of PhysiologyDartmouth Medical SchoolLebanon
  3. 3.Department of Physiology, School of Medical SciencesUniversity of BristolBristolUK
  4. 4.GRAP-JE-UFR de PharmacieAmiensFrance

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