Genetic inactivation of Kcnj16 identifies Kir5.1 as an important determinant of neuronal PCO2/pH sensitivity.
The molecular identity of ion channels which confer PCO(2)/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 CO(2) 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 PCO(2)/pH sensitivity in locus coeruleus neurons and suggest that Kir5.1 may be involved in the response to hypercapnic acidosis.
Section of Human Physiology, University of Perugia School of Medicine, Perugia 06100, Italy.
M Cristina
MC
D'Adamo
Lijun
L
Shang
Paola
P
Imbrici
Steve D M
SD
Brown
Mauro
M
Pessia
Stephen J
SJ
Tucker
D000138:Acidosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D004553:Electric Conductivity; D005260:Female; D017353:Gene Deletion; D006863:Hydrogen-Ion Concentration; D008125:Locus Coeruleus / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency* / Q000235:genetics*; D000097062:Kir5.1 Channel
D002245:Carbon Dioxide; D024661:Potassium Channels, Inwardly Rectifying; D000097062:Kir5.1 Channel