Intracellular pH regulation of neurons in chemosensitive and nonchemosensitive areas of brain slices

Abstract

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⁻/HCO₃⁻ 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 CO₂/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 CO₂/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 CO₂/H⁺ response of chemosensitive neurons.