Maintenance of the Respiratory Rhythm during Normoxia and Hypoxia

  • Diethelm W. Richter
  • Mark C. Bellingham
  • Christian Schmidt


The generation and maintenance of respiratory rhythm is currently the subject of some controversy, with several theories available for its’ origin, based on experimental results from in vivo 1 and in vitro preparations.2-5 While there appear to be some age-dependent differences in rhythm generation mechanisms,5-8 there is little question that synaptic interconnection between different neuronal groups in the medulla oblongata plays a vital part in generating and shaping respiratory pattern in adult mammals.9 Such synaptic interconnections are likely to be mainly inhibitory in nature.10-12 Intrinsic membrane properties of certain types of respiratory neurons2, 3, 13–17 may also underlie key mechanisms for phase transitions. Together the two processes constitute the core rhythm generator for respiration.18, 19


Respiratory Rhythm Respiratory Neuron Intracellular Injection Phrenic Nerve Activity Intrinsic Membrane Property 
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  1. 1.
    D.W. Richter, D. Ballantyne and J.E. Remmers, How is the respiratory rhythm generated? A model, NIPS 1:109(1986).Google Scholar
  2. 2.
    H. Onimaru and I. Homma, Respiratory rhythm generator neurons in medulla of brainstem-spinal cord preparation from newborn rat, Brain Res. 403:380(1987).PubMedCrossRefGoogle Scholar
  3. 3.
    H. Onimaru, A. Arata and I. Homma, Primary respiratory rhythm generator in the medulla of brainstem-spinal cord preparation from newborn rat, Brain Res. 445:314 (1988).PubMedCrossRefGoogle Scholar
  4. 4.
    J.L. Feldman and J.C. Smith, Cellular mechanisms underlying modulation of breathing pattern in mammals, Ann. N. Y. Acad. Sci. 563:114 (1989).PubMedCrossRefGoogle Scholar
  5. 5.
    J.C. Smith, J.J. Greer, G. Liu and J.L. Feldman, Neural mechanisms generating respiratory pattern in mammalian brain stem-spinal cord in vitro. I. Spatiotemporal patterns of motor and medullary neuron activity, J. Neurophysiol. 64:1149 (1990).PubMedGoogle Scholar
  6. 6.
    J.C. Smith, H.H. Ellenberger, K. Ballanyi, D.W. Richter and J.L. Feldman, A brainstem region that may generate respiratory rhythm in mammals, Science 254:726 (1991).PubMedCrossRefGoogle Scholar
  7. 7.
    D.W. Richter and K.M. Spyer, Cardio-respiratory control, in: “Central Regulation of Autonomic Functions”, A.D. Loewy and K.M. Spyer, eds., Oxford University Press, Oxford (1990).Google Scholar
  8. 8.
    D.W. Richter, K.M. Spyer, M.P. Gilbey, E.E. Lawson, C.R. Bainton and Z. Wilhelm, On the existence of a common cardiorespiratory network, in: “Cardiorespiratory and Motor Coordination”, H.P. Koepchen and T. Huopaniemi, eds., Springer-Verlag, Munich (1991).Google Scholar
  9. 9.
    D.W. Richter, Generation and maintenance of the respiratory rhythm, J. Exp. Biol. 100:93 (1982).PubMedGoogle Scholar
  10. 10.
    D.W. Richter, H. Camerer, M. Meesmann and N. Röhrig, Studies on the synaptic interconnection between bulbar respiratory neurones of cats, Pflügers Arch. 380:245 (1979).PubMedCrossRefGoogle Scholar
  11. 11.
    D. Ballantyne and D.W. Richter, Postsynaptic inhibition of bulbar inspiratory neurones in the cat, J. Physiol. (Lond.) 348:67 (1984).Google Scholar
  12. 12.
    D. Ballantyne and D.W. Richter, The non-uniform character of expiratory synaptic activity in expiratory bulbospinal neurones of the cat, J. Physiol. (Lond.) 370:433 (1986).Google Scholar
  13. 13.
    S.W. Mifflin, D. Ballantyne, S.B. Backman and D.W. Richter, Evidence for a calcium activated potassium conductance in medullary respiratory neurones, in: “Neurogenesis of Central Respiratory Rhythm”, A.L. Bianchi and M. Denavit-Saubie, eds., MTP Press, Lancaster (1985).Google Scholar
  14. 14.
    S.W. Mifflin and D.W. Richter, The effect of QX-314 on medullary respiratory neurones, Brain Res. 420:22 (1987).PubMedCrossRefGoogle Scholar
  15. 15.
    J. Champagnat, T. Jacquin and D.W. Richter, Voltage-dependent currents in neurones of the nuclei of the solitary tract of rat brainstem slices, Pflügers Arch. 406:372(1986).PubMedCrossRefGoogle Scholar
  16. 16.
    M.S. Dekin and P.A. Getting, In vitro characterization of neurons in the ventral part of the nucleus tractus solitarius. II. Ionic basis for repetitive firing patterns, J. Neurophysiol. 58:215 (1987).PubMedGoogle Scholar
  17. 17.
    D.W. Richter, J. Champagnat and S.W. Mifflin, Membrane properties of medullary respiratory neurones of the cat, in: “Respiratory Muscles and their Neuromotor Control”, G.C. Sieck, S.C. Gandevia and W.E. Cameron, eds., Alan R. Liss, New York (1987).Google Scholar
  18. 18.
    D.W. Richter, D. Ballantyne and S.W. Mifflin, Interaction between postsynaptic activities and membrane properties in medullary respiratory neurones, in: “Neurogenesis of Central Respiratory Rhythm”, A.L. Bianchi and M. Denavit-Saubie, eds., MTP Press, Lancaster (1985).Google Scholar
  19. 19.
    D.W. Richter, J. Champagnat and S.W. Mifflin, Membrane properties involved in respiratory rhythm generation, in: “Neurobiology of the Control of Breathing”, C. von Euler and H. Lagercrantz, eds., Raven Press, New York (1986).Google Scholar
  20. 20.
    S. Long and J. Duffin, The neuronal determinants of respiratory rhythm, Prog. Neurobiol. 27:101 (1986).PubMedCrossRefGoogle Scholar
  21. 21.
    J. Duffin and D. Aweida, The propriobulbar respiratory neurons in the cat, Exp. Brain Res. 81:213 (1990).PubMedCrossRefGoogle Scholar
  22. 22.
    K. Ezure, Synaptic connections between medullary respiratory neurons and considerations on the genesis of respiratory rhythm, Prog. Neurobiol. 35:429(1990).PubMedCrossRefGoogle Scholar
  23. 23.
    S.M. Botros and E.N. Bruce, Neural network implementation of the three-phase model of respiratory rhythm generation, Biol. Cybern. 63:143(1990).PubMedCrossRefGoogle Scholar
  24. 24.
    A.I. Pack and D.W. Richter, Modelling cardio-respiratory activities, Eur. J. Neurosci. Suppl. 3:172 (1990).Google Scholar
  25. 25.
    R. Nesland and F. Plum, Subtypes of medullary respiratory neurons, Exp. Neurol. 12:337 (1963).CrossRefGoogle Scholar
  26. 26.
    M.I. Cohen, Discharge patterns of brain-stem respiratory neurons during Hering-Breuer reflex evoked by lung inflation, J. Neurophysiol. 32:356(1969).PubMedGoogle Scholar
  27. 27.
    S.W. Schwarzacher, J.C. Smith and D.W. Richter, Respiratory neurones in the pre-Bötzinger region of cats, Pflügers Arch. 418:R17 (1991).Google Scholar
  28. 28.
    E. Carbone and H.D. Lux, Kinetics and selectivity of a low-voltage-activated calcium current in chick and rat sensory neurones, J. Physiol. (Lond.) 386:547 (1987).Google Scholar
  29. 29.
    H. Meves and W. Vogel, Calcium inward currents in internally perfused giant axons, J. Physiol. (Lond.) 235:225 (1973).Google Scholar
  30. 30.
    C.E. Stafstrom, P.C. Schwindt, M.C. Chubb and W.E. Crill, Properties of persistent sodium conductance and calcium conductance of layer V neurons from cat sensorimotor cortex in vitro, J. Neurophysiol. 53:153(1985).PubMedGoogle Scholar
  31. 31.
    R.W. Tsien, D. Lipscombe, D.V. Madison, K.R. Bley and A.P. Fox, Multiple types of neuronal calcium channels and their selective modulation, TINS 11:431(1988).PubMedGoogle Scholar
  32. 32.
    L.D. Partridge and D. Swandulla, Calcium-activated non-specific cation channels, TINS 11:69 (1988).PubMedGoogle Scholar
  33. 33.
    A. Marty, Ca+-dependent K+ channels with large unitary conductance, TINS 6:262 (1983).Google Scholar
  34. 34.
    N. Fujiwara, H. Higashi, K. Shimoji and M. Yoshimura, Effects of hypoxia on rat hippocampal neurones in vitro, J. Physiol. (Lond.) 384:131 (1987).Google Scholar
  35. 35.
    E. Cherubini, Y. Ben-Ari and K. Krnjevic, Anoxia produces smaller changes in synaptic transmission, membrane potential, and input resistance in immature rat hippocampus, J. Neurophysiol. 62:882 (1989).PubMedGoogle Scholar
  36. 36.
    D.W. Richter, A. Bischoff, K. Anders, M.C. Bellingham and U. Windhorst, Hypoxia induced changes of the respiratory network of cats, J. Physiol. (Lond.) 443:1 (1991).Google Scholar
  37. 37.
    M.C. Bellingham, C. Schmidt, U. Windhorst and D.W. Richter, Effects of hypoxia on postsynaptic potentials in medullary respiratory neurons of the cat, Soc. Neurosci. Abstr. 17:104 (1991).Google Scholar
  38. 38.
    T. Hedner, J. Hedner, P. Wessberg and J. Jonason, Regulation of breathing in the rat: indications for a role of central adenosine mechanisms, Neurosci. Lett. 33:147(1982).PubMedCrossRefGoogle Scholar
  39. 39.
    M. Runold, H. Lagercrantz, N.R. Prabhakar and B.B. Fredholm, Role of adenosine in hypoxic ventilatory depression, J. Appl. Physiol. 67:541(1989).PubMedGoogle Scholar
  40. 40.
    D.E. Millhorn, F.L. Eldridge and T.G. Waldrop, Prolonged stimulation of respiration by endogenous central serotonin, Resp. Physiol. 42:171(1980).CrossRefGoogle Scholar
  41. 41.
    M.M. Grunstein, T.A. Hazinski and H.A. Schlueter, Respiratory control during hypoxia in newborn rabbits: implied action of endorphins, J. Appl. Physiol. 51:122 (1981).PubMedGoogle Scholar
  42. 42.
    K. Iverson, T. Hedner and P. Lundborg, GABA concentrations and turn-over in neonatal rat brain during asphyxia and recovery, Acta Physiol. Scand. 118:91 (1983).CrossRefGoogle Scholar
  43. 43.
    B.S. Meldrum, Excitatory amino acids and anoxic/ischaemic brain damage, TINS 8:47 (1985).Google Scholar
  44. 44.
    T.W. Stone, Physiological roles for adenosine and adenosine 5’-triphosphate in the nervous system, Neurosci. 6:523(1981).CrossRefGoogle Scholar
  45. 45.
    T.V. Dunwiddie, The physiological role of adenosine in the central nervous system, Int. Rev. Neurobiol. 27:63 (1985).PubMedCrossRefGoogle Scholar
  46. 46.
    T.V. Dunwiddie, C.R. Lupica and W.R. Proctor, Unitary EPSPs measured by whole-cell recording are reduced by adenosine in rat hippocampal CA1 pyramidal neurons in vitro, Soc. Neurosci. Abstr. 17:1548(1991).Google Scholar
  47. 47.
    C. Schmidt, M.C. Bellingham and D.W. Richter, Effects of intracellular injection of adenosine in medullary respiratory neurons of cat, Pflügers Arch. 420, Suppl. 1: R130 (1992).Google Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Diethelm W. Richter
    • 1
  • Mark C. Bellingham
    • 1
  • Christian Schmidt
    • 1
  1. 1.II. Physiology InstituteUniversity of GöttingenGöttingenGermany

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