Differential effects of carbon dioxide and pH on central chemoreceptors in the rat in vitro.

The brain stem, cervical cord and attached phrenic nerve were excised from neonatal rats and superfused in vitro. Respiratory activity was recorded from the phrenic nerve following transection of all the cranial nerves and dorsal roots. The frequency of spontaneous periodic activity recorded from the phrenic nerve was 6‐14/min during superfusion with a saline solution equilibrated with 5% CO2 in O2 at 25 degrees C (pH 7.3). The magnitude of respiration was estimated from the peak value of phrenic activity integrated for each 0.1 s period. When the pH of the superfusion fluid was altered by changing the HCO3‐concentration at constant PCO2, respiratory activity increased in low pH and decreased in high pH. These changes were maintained as long as a given pH was held. Respiratory changes observed under these conditions were characterized by alterations in both respiratory frequency and magnitude. When the CO2 level of the superfusion fluid was altered, maintaining constant pH by modified HCO3‐concentrations, respiratory activity increased at high PCO2 and decreased at low PCO2. These changes were transient and lasted only for a few minutes after exposure to a new level of PCO2. Respiratory changes observed under these conditions were characterized by alterations in magnitude but not in frequency. At constant PCO2 an increase in the HCO3‐concentration occasionally enhanced the magnitude of respiration before respiratory activity was depressed by the increased pH. This suggests that HCO3‐ may act independently as a stimulus to the central chemoreceptor. It is concluded that the mammalian central chemoreceptor for respiratory control is responsive independently to H+ and CO2 and that H+ and CO2 exert differential effects on the respiratory centre in terms of frequency and magnitude. It is suggested that frequency modulation and magnitude (tidal volume) modulation for respiratory control are triggered at different regions in the respiratory centre and/or rely on different mechanisms.

[1]  玉井 直.  A pharmacological study on respiratory rhythm in the isolated brainstem-spinal cord preparation of the newborn rat , 1986 .

[2]  M. Kuno,et al.  Central chemosensitivity to H+ and CO2 in the rat respiratory center in vitro , 1985, Brain Research.

[3]  J. Kiley,et al.  Respiratory responses to medullary hydrogen ion changes in cats: different effects of respiratory and metabolic acidoses. , 1985, The Journal of physiology.

[4]  J. Kiley,et al.  Respiratory effects of carbon dioxide‐induced changes of medullary extracellular fluid pH in cats. , 1984, The Journal of physiology.

[5]  T. Suzue,et al.  Respiratory rhythm generation in the in vitro brain stem‐spinal cord preparation of the neonatal rat. , 1984, The Journal of physiology.

[6]  P. Barts,et al.  Effects of respiratory and (isocapnic) metabolic arterial acid-base disturbances on medullary extracellular fluid pH and ventilation in cats. , 1983, Respiration physiology.

[7]  T. Murakoshi,et al.  Electrophysiology of reflexes in an isolated brainstem-spinal cord preparation of the newborn rat , 1983 .

[8]  H. Folgering,et al.  Dynamics of brain extracellular fluid pH and phrenic nerve activity in cats after end-tidal CO2 forcing. , 1982, Respiration physiology.

[9]  H. Loeschcke.  Central chemosensitivity and the reaction theory. , 1982, The Journal of physiology.

[10]  J. A. Holloway,et al.  Neurophysiological studies on superficial medullary chemosensitive area for respiration , 1982, Brain Research.

[11]  M. Schlaefke.  Central chemosensitivity: a respiratory drive. , 1981, Reviews of physiology, biochemistry and pharmacology.

[12]  P. Quanjer,et al.  Influence of the CSF bicarbonate concentration on the ventilatory response to CO2 in relation to the location of the central chemoreceptors. , 1978, Respiration physiology.

[13]  P. Cragg,et al.  The pH of brain extracellular fluid in the cat , 1977, The Journal of physiology.

[14]  R. Thomas.  The effect of carbon dioxide on the intracellular pH and buffering power of snail neurones. , 1976, The Journal of physiology.

[15]  F. Eldridge,et al.  Relationship between respiratory nerve and muscle activity and muscle force output. , 1975, Journal of applied physiology.

[16]  D. McCloskey,et al.  The responses of carotid body chemoreceptors in the cat to sudden changes of hypercapnic and hypoxic stimuli. , 1971, Respiration physiology.

[17]  F. Eldridge.  Relationship between phrenic nerve activity and ventilation. , 1971, The American journal of physiology.

[18]  H. Loeschcke,et al.  Ventilatory response to alterations of H+ ion concentration in small areas of the ventral medullary surface. , 1970, Respiration physiology.

[19]  L. Leitner,et al.  Carotid chemoreceptor response to intermittent or sustained stimulation in the cat. , 1969, Respiration physiology.

[20]  P. C. Tang,et al.  Brain stem control of respiratory depth and rate in the cat. , 1967, Respiration physiology.

[21]  J. Pappenheimer.  The ionic composition of cerebral extracellular fluid and its relation to control of breathing. , 1967, Harvey lectures.

[22]  J. Severinghaus,et al.  REGIONS OF RESPIRATORY CHEMOSENSITIVITY ON THE SURFACE OF THE MEDULLA * , 1963 .

[23]  C. Eyzaguirre,et al.  Chemoreceptor activity of the carotid body of the cat , 1961, The Journal of physiology.

[24]  I. Leusen.  Chemosensitivity of the respiratory center influence of changes in the H+ and total buffer concentrations in the cerebral ventricles on respiration. , 1953, The American journal of physiology.

[25]  I. Leusen.  Chemosensitivity of the respiratory center; influence of CO2 in the cerebral ventricles on respiration. , 1954, The American journal of physiology.

[26]  R. Gesell,et al.  A COMPARISON OF MOTOR INTEGRATION IN THE MOUSE, RAT, RABBIT, DOG AND HORSE , 1943 .