Intracellular pH regulation in neurons from chemosensitive and nonchemosensitive areas of the medulla

Intracellular pH (pH_i) regulation was studied in neurons from two chemosensitive [nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM)] and two nonchemosensitive [hypoglossal (Hyp) and inferior olive (IO)] areas of the medulla oblongata. Intrinsic buffering power (β_int) was the same in neurons from all regions (46 mM/pH U). Na⁺/H⁺exchange mediated recovery from acidification in all neurons [Ritucci, N. A., J. B. Dean, and R. W. Putnam.Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol.42): R433–R441, 1997]. Cl⁻/${HCO}_3^{-}$ exchange mediated recovery from alkalinization in VLM, Hyp, and IO neurons but was absent from most NTS neurons. The Na⁺/H⁺exchanger from NTS and VLM neurons was fully inhibited when extracellular pH (pH_o) <7.0, whereas the exchanger from Hyp and IO neurons was fully inhibited only when pH_o <6.7. The Cl⁻/${HCO}_3^{-}$ exchanger from VLM, but not Hyp and IO neurons, was inhibited by pH_o of 7.9. These pH regulatory properties resulted in steeper pH_i-pH_orelationships in neurons from chemosensitive regions compared with those from nonchemosensitive regions. These differences are consistent with a role for changes of pH_i as the proximate signal in central chemoreception and changes of pH_o in modulating pH_i changes.