brain stem; central chemoreceptor; carbon dioxide; fluorescence imaging; respiration; Na ϩ /H ϩ exchange THE LEVEL OF CO 2 /H ϩ in the blood is carefully regulated by certain neurons in several areas of the medulla oblongata. These neurons are collectively known as central chemoreceptors. The areas in which these neurons are located are known as chemosensitive areas and include the ventrolateral medulla (VLM), the nucleus of the solitary tract (NTS), and the medullary raphe (16). It is hypothesized that an increased level of CO 2 /H ϩ stimulates the central chemoreceptors, which in turn, via the respiratory central pattern generator neurons (which they presumably innervate), increase ventilation (8). The stimulus to the central chemoreceptors has been the subject of much debate. It has been hypothesized that the stimulus may be an increase in molecular CO 2 , a decrease in extracellular pH (pH o ), a decrease in intracellular pH (pH i ), or a combination of any of the three (1,7,16,24,25,30). We have previously shown that both pH i and pH o may play a role in central chemosensitivity (22).It would seem logical that if a change in pH is the major signaling pathway by which central chemoreceptors monitor a change in blood CO 2 /H ϩ , the manner in which these cells respond to acid/base disturbances should be different from that of cells that are not chemoreceptors (nonchemoreceptors). In a previous study, we found that Na ϩ /H ϩ exchange is the only pH i -regulating mechanism involved during recovery from intracellular acidification in neurons from both chemosensitive (NTS and VLM) and nonchemosensitive [hypoglossal nucleus (Hyp) and inferior olive (IO)] areas of the medulla (22). We also found that neurons from chemosensitive areas (NTS and VLM) respond with a maintained intracellular acidification during hypercapnic acidosis, but exhibit pH i recovery during isohydric hypercapnia. This is in contrast to neurons from nonchemosensitive areas (Hyp and IO) that exhibit pH i recovery even during hypercapnic acidosis (22). These findings suggest that the Na ϩ /H ϩ exchanger is more easily inhibited by a decrease of pH o in neurons from chemosensitive areas versus nonchemosensitive areas.The major aim of the present study was to examine pH i regulation in greater detail in individual neurons from chemosensitive and nonchemosensitive areas of the medulla to investigate whether other differences in pH i regulation are present. It must be noted that these data are from neurons in known chemosensitive areas (16) but that the individual neurons themselves may or may not be chemoreceptors. Our data show the following: 1) intrinsic buffering power (␤ int ) is the same in all neurons tested; 2) removal of extracellular chloride at steady-state pH i results in intracellular alkalinization in all Hyp, IO, and VLM neurons but results in intracellular acidification in most NTS neurons, suggesting that Cl Ϫ /HCO 3 Ϫ exchange is present in all Hyp, IO, and VLM neurons but not in most NTS neurons; 3) steady-state pH i is more depende...

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2016-11-15T19:40:59