The roles of medullary extracellular and cerebrospinal fluid pH in control of respiration.

To determine the effective stimulus to the central chemoreceptors, we measured CSF and medullary extracellular fluid (ECF) pH and phrenic activity in 11 anesthetized, paralyzed, vagotomized and glomectomized cats. Flat-tipped pH electrodes (2 mm diam.) were used to measure ECF pH on the ventral surface of the medulla and CSF pH 2 mm above the surface. Changes in alveolar/arterial PCO2 were produced by airway occlusions of 10-20 sec durations. Changes in CSF PCO2 and pH were made by infusing 100% CO2 or an acid buffer into the CSF. Airway occlusion caused an increase of alveolar/arterial PCO2. ECF pH began to fall 6-10 sec later, with a maximum decrease of 0.032 pH unit at 21.9 sec. Phrenic activity increased as ECF pH decreased, the greatest activity occurring when ECF pH was most acid. CSF pH decreased after a longer delay. Its maximum decrease at 54.1 sec was smaller (0.026 pH unit) than ECF pH and did not correlate with the increase of phrenic activity. Addition of 100% CO2 or an acid buffer into the CSF produced an acid shift in the CSF pH but no change in ECF pH or phrenic activity. Prolonged (greater than 30 min) increase of acidity of CSF did not alter phrenic activity until ECF pH developed a delayed acid shift. Even then, the change of ECF pH was much smaller than that of CSF. We conclude that medullary chemoreceptors do not respond to changes of CSF pH or PCO2 and that change of pH of CSF minimally affects ECF pH. On the other hand, respiratory responses are closely linked to changes in ECF pH.