Intracellular pH Regulation of Neurons in Chemosensitive and Nonchemosensitive Areas of Brain Slices

The role of changes of intracellular pH (pH _i ) as the proximal signal in central chemosensitive neurons has been studied. pH _i recovery from acidification is mediated by Na ⁺ /H ⁺ exchange in all medullary neurons and pH _i recovery from alkalinization is mediated by Cl ⁻ /HCO ₃ ⁻ exchange in most medullary neurons. These exchangers are more sensitive to inhibition by changes in extracellular pH (pH _o ) in neurons from chemosensitive regions compared to those from nonchemosensitive regions. Thus, neurons from chemosensitive regions exhibit a maintained intracellular acidification in response to hypercapnic acidosis but they show pH _i recovery in response to isohydric hypercapnia. A similar pattern of pH _i response is seen in other CO ₂ /H ⁺ -responsive cells, including glomus cells, sour taste receptor cells, and chemosensitive neurons from snails, suggesting that a maintained fall of pH _i is a common feature of the proximal signal in all CO ₂ /H ⁺ -sensitive cells. To further evaluate the potential role of pH _i changes as proximal signals for chemosensitive neurons, studies must be done to: determine why a lack of pH _i recovery from hypercapnic acidosis is seen in some nonchemosensitive neurons; establish a correlation between hypercapnia-induced changes of pH _i and membrane potential (V _m ); compare the hypercapnia-induced pH _i changes seen in neuronal cell bodies with those in dendritic processes; understand why the V _m response to hypercapnia of many chemosensitive neurons is washed out when using whole cell patch pipettes; and employ knock out mice to investigate the role of certain proteins in the CO ₂ /H ⁺ response of chemosensitive neurons.