Genetic Inactivation of Kcnj16 Identifies Kir5.1 as an Important Determinant of Neuronal PCO2/pH Sensitivity

• Published in: The Journal of biological chemistry 2011-01, Vol.286 (1), p.192-198
• Main Authors: D'Adamo, M. Cristina, Shang, Lijun, Imbrici, Paola, Brown, Steve D.M., Pessia, Mauro, Tucker, Stephen J.
• Format: Article
• Language: English
• Subjects: Acidosis - metabolism; Acidosis - pathology; Animals; Carbon Dioxide - pharmacology; Electric Conductivity; Female; Gene Deletion; Gene Knockout; Hydrogen-Ion Concentration; Ion Channels; Kir Channel; Kir4.1/Kir5.1; Kir5.1 Channel; Locus Coeruleus - cytology; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Neurons - drug effects; Neurons - metabolism; Neuroscience; pH-sensitive; Potassium Channels; Potassium Channels, Inwardly Rectifying - deficiency; Potassium Channels, Inwardly Rectifying - genetics; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.189290

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.