Genetic Inactivation of Kcnj16 Identifies Kir5.1 as an Important Determinant of Neuronal PCO2/pH Sensitivity
Genetic Inactivation of Kcnj16 Identifies Kir5.1 as an Important Determinant of Neuronal PCO2/pH Sensitivity
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DOI：
10.1074/jbc.m110.189290
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发表时间：
2011-01-07
影响因子：
4.8
通讯作者：
Tucker, Stephen J.
中科院分区：
文献类型：
--
作者：
D'Adamo, M. Cristina;Shang, Lijun;Tucker, Stephen J.
在脑中赋予PCO 2/pH敏感性的离子通道的分子身份尚不清楚。异聚Kir4.1/Kir5.1通道对细胞内pH的抑制高度敏感，并广泛表达于参与心肺控制的几个脑干核团，包括蓝斑。因此，这导致了一个建议的作用，这些通道在神经元的CO2化学敏感性。为了检验这一点，我们产生了缺乏Kir5.1（Kcnj 16）基因的突变小鼠。我们发现，尽管Kcnj 16（（+/+））小鼠的蓝斑神经元对细胞质碱化和酸化反应迅速，但Kcnj 16（（-/-））小鼠的蓝斑神经元显示出显著降低和延迟的反应。这些结果表明Kir5.1是蓝斑神经元PCO 2/pH敏感性的重要决定因素，并表明Kir5.1可能参与了对高碳酸酸中毒的反应。
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.