Genetic inactivation of Kcnj16 identifies Kir5.1 as an important determinant of neuronal PCO2/pH sensitivity
D'Adamo, M.C. ; Shang, Lijun ; Imbrici, P. ; Brown, S.D.M. ; Pessia, M. ; Tucker, S.J.
D'Adamo, M.C.
Shang, Lijun
Imbrici, P.
Brown, S.D.M.
Pessia, M.
Tucker, S.J.
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2011
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Abstract
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.
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D'Adamo MC, Shang L, Imbrici P, Brown SD, Pessia M and Tucker SJ (2011) Genetic inactivation of Kcnj16 identifies Kir5.1 as an important determinant of neuronal PCO2/pH sensitivity. Journal of Biological Chemistry. 286(1): 192-198.
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