Is central chemoreceptor sensitive to intracellular rather than extracellular pH?

Area of Science:

• Neuroscience
• Respiratory Physiology
• Acid-Base Balance

Background:

• The chemosensitive area on the ventral brain stem regulates ventilation in response to local pH.
• Traditionally, extracellular fluid hydrogen ion concentration ([pH]e) is considered the primary stimulus.
• Recent findings suggest intracellular pH ([pH]i) may also be a significant factor.

Purpose of the Study:

• To investigate the role of intracellular pH ([pH]i) in the chemosensitive response.
• To differentiate the effects of CO2 and acetazolamide on [pH]e and [pH]i.
• To determine the contribution of cerebral blood flow (CBF) acidosis to acetazolamide-induced CBF changes.

Main Methods:

• Administration of acetazolamide to dissociate [pH]e and [pH]i.
• Measurement of cerebrospinal fluid pH ([pH]c) and cerebral blood flow (CBF).
• Comparison of acetazolamide effects with CO2 breathing.
• Utilizing Magnetic Resonance (MR) spectroscopy to assess [pH]i in animal models and humans.

Main Results:

• Acetazolamide causes a significant acid shift in CSF pH ([pH]c) and a marked increase in CBF.
• The increase in CBF induced by acetazolamide is quantitatively accounted for by CBF acidosis.
• CO2 breathing decreases both [pH]e and [pH]i, while acetazolamide does not significantly decrease [pH]i when hypercapnia is prevented.

Conclusions:

• Cerebral blood flow acidosis can explain the CBF increase observed with acetazolamide.
• Acetazolamide and CO2 differentially affect intracellular pH ([pH]i).
• Intracellular pH ([pH]i) may be a critical determinant in chemosensory responses, challenging the sole reliance on extracellular pH ([pH]e).