Is central chemoreceptor sensitive to intracellular rather than extracellular pH?

The chemosensitive area on the ventral surface of the brain stem responds to local acidosis by eliciting hyperventilation and to local alkalosis by hypoventilation. The stimulus is conventionally thought to be the hydrogen ion concentration in the area's extracellular fluid. It is pointed out, however, that the elegant studies by Loeschcke & Ahmad have demonstrated that [pH]e and [pH]i are normally tightly and rapidly coupled (Loeschcke & Ahmad, 1980). For this reason, the stimulus might just as well be the intracellular hydrogen ion concentration in the chemoreceptor area. The administration of acetazolamide allows the dissociation of [pH]e from [pH]i. With acetazolamide a sharp acid shift of CSF pH [( pH]c) is measured and in two consonance with this shift a marked increase in CBF is seen. Comparing these two reactions to that obtained with CO2 breathing, it is apparent that 7% CO2 causes about the same decrease in [pH]e and the same increase in CBF. In other words CBF acidosis can quantitatively account for the CBF increase induced by acetazolamide. But CO2 and acetazolamide influence [pH]i quite differently, as CO2 drops [pH]i to almost the same extent as [pH]c, while two recent studies by MR spectroscopy have shown that acetazolamide does not drop [pH]i measurably, if tissue hypercapnia is prevented in artificially ventilated rabbits or by the mild spontaneous hyperventilation caused by acetazolamide in normal man.(ABSTRACT TRUNCATED AT 250 WORDS)