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.