title: Phox2b-expressing retrotrapezoid neurons are intrinsically responsive to H+ and CO2.
abstract: Central respiratory chemoreceptors sense changes in CO2/H(+) and initiate the adjustments to ventilation required to preserve brain and tissue pH. The cellular nature of the sensors (neurons and/or glia) and their CNS location are not conclusively established but the glutamatergic, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) are strong candidates. However, a direct demonstration that RTN neurons are intrinsically sensitive to CO2/H(+), required for designation as a chemosensor, has been lacking. To address this, we tested the pH sensitivity of RTN neurons that were acutely dissociated from two lines of Phox2b-GFP BAC transgenic mice. All GFP-labeled cells assayed by reverse transcriptase-PCR (n = 40) were Phox2b+, VGlut2+, TH-, and ChAT-, the neurochemical phenotype previously defined for chemosensitive RTN neurons in vivo. We found that most dissociated RTN neurons from both lines of mice were CO2/H(+)-sensitive (∼79%), with discharge increasing during acidification and decreasing during alkalization. The pH-sensitive cells could be grouped into two populations characterized by similar pH sensitivity but different basal firing rates, as previously observed in recordings from GFP-labeled RTN neurons in slice preparations. In conclusion, these data indicate that RTN neurons are inherently pH-sensitive, as expected for a respiratory chemoreceptor.
authors: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors: Sheng
authors: S
authors: Wang
authors: Yingtang
authors: Y
authors: Shi
authors: Shaofang
authors: S
authors: Shu
authors: Patrice G
authors: PG
authors: Guyenet
authors: Douglas A
authors: DA
authors: Bayliss
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002245:Carbon Dioxide / Q000494:pharmacology*; D002628:Chemoreceptor Cells / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D011522:Protons; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D011522:Protons; D012333:RNA, Messenger; C493475:Slc17a6 protein, rat; D014157:Transcription Factors; D050599:Vesicular Glutamate Transport Protein 2; D002245:Carbon Dioxide; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
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