Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons

Robert W. Putnam, Jessica A. Filosa, Nicola A. Ritucci

Research output: Contribution to journalReview articlepeer-review

226 Scopus citations


An increase in CO2/H+ is a major stimulus for increased ventilation and is sensed by specialized brain stem neurons called central chemosensitive neurons. These neurons appear to be spread among numerous brain stem regions, and neurons from different regions have different levels of chemosensitivity. Early studies implicated changes of pH as playing a role in chemosensitive signaling, most likely by inhibiting a K+ channel, depolarizing chemosensitive neurons, and thereby increasing their firing rate. Considerable progress has been made over the past decade in understanding the cellular mechanisms of chemosensitive signaling using reduced preparations. Recent evidence has pointed to an important role of changes of intracellular pH in the response of central chemosensitive neurons to increased CO 2/H+ levels. The signaling mechanisms for chemosensitivity may also involve changes of extracellular pH, intracellular Ca2+, gap junctions, oxidative stress, glial cells, bicarbonate, CO2, and neurotransmitters. The normal target for these signals is generally believed to be a K+ channel, although it is likely that many K+ channels as well as Ca2+ channels are involved as targets of chemosensitive signals. The results of studies of cellular signaling in central chemosensitive neurons are compared with results in other CO2- and/or H+-sensitive cells, including peripheral chemoreceptors (carotid body glomus cells), invertebrate central chemoreceptors, avian intrapulmonary chemoreceptors, acid-sensitive taste receptor cells on the tongue, and pain-sensitive nociceptors. A multiple factors model is proposed for central chemosensitive neurons in which multiple signals that affect multiple ion channel targets result in the final neuronal response to changes in CO 2/H+.

Original languageEnglish (US)
Pages (from-to)C1493-C1526
JournalAmerican Journal of Physiology - Cell Physiology
Issue number6 56-6
StatePublished - Dec 2004
Externally publishedYes


  • Brain stem
  • Calcium
  • Carbonic anhydrase
  • Channel
  • Gap junction
  • Glia
  • Glomus
  • Hypercapnia
  • Nociception
  • Peripheral chemoreceptor
  • Potassium
  • Taste receptor
  • Ventilation

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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