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.