Genetic inactivation of Kcnj16 identifies Kir5.1 as an important determinant of neuronal PCO2/pH sensitivity

M. Cristina D'Adamo, Lijun Shang, Paola Imbrici, Steve D.M. Brown, Mauro Pessia, Stephen J. Tucker

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

The molecular identity of ion channels which confer PCO2/pH sensitivity in the brain is unclear. Heteromeric Kir4.1/Kir5.1 channels are highly sensitive to inhibition by intracellular pH and are widely expressed in several brainstem nuclei involved in cardiorespiratory control, including the locus coeruleus. This has therefore led to a proposed role for these channels in neuronal CO2 chemosensitivity. To examine this, we generated mutant mice lacking the Kir5.1 (Kcnj16) gene. We show that although locus coeruleus neurons from Kcnj16(+/+) mice rapidly respond to cytoplasmic alkalinization and acidification, those from Kcnj16(-/-) mice display a dramatically reduced and delayed response. These results identify Kir5.1 as an important determinant of PCO2/pH sensitivity in locus coeruleus neurons and suggest that Kir5.1 may be involved in the response to hypercapnic acidosis.

Original languageEnglish
Pages (from-to)192-198
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number1
DOIs
Publication statusPublished - Jan 7 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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