Lack of the Kir4.1 channel subunit abolishes K+ buffering properties of astrocytes in the ventral respiratory group:: Impact on extracellular K+ regulation
Lack of the Kir4.1 channel subunit abolishes K+ buffering properties of astrocytes in the ventral respiratory group:: Impact on extracellular K+ regulation
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DOI：
10.1152/jn.00996.2005
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发表时间：
2006-03-01
影响因子：
2.5
通讯作者：
Hülsmann, S
中科院分区：
文献类型：
--
作者：
Neusch, C;Papadopoulos, N;Hülsmann, S
脑干腹侧呼吸群（VRG）神经元的持续节律性活动导致细胞外K+的周期性变化。为了估计弱内向整流K+通道Kir4.1（KCNJ 10）在细胞外K+清除中的参与，我们研究了其在呼吸网络星形胶质细胞中的功能表达。Kir4.1在VRG的星形胶质细胞中表达，主要在毛细血管周围的精细星形胶质细胞过程中，并与VRG神经元非常接近。Kir4.1表达在出生后早期发育过程中上调。使用Kir4.1通道基因中具有无效突变的小鼠研究星形胶质细胞Kir4.1的生理作用，所述小鼠与在其星形胶质细胞中表达增强的绿色荧光蛋白的转基因小鼠杂交。Kir4.1（-/-）小鼠星形胶质细胞膜电位去极化，Ba ~（2+）敏感性内向K ~+电流减弱。来自Kir4.1（-/-）小鼠的脑切片，含有产生呼吸节律的前Botzinger复合物，与野生型对照相比，在节律爆发活动中没有显示出任何明显的差异，表明单独缺乏Kir4.1通道不会损害呼吸网络活动。细胞外K+测量显示Kir4.1通道有助于细胞外K+调节。Kir4.1通道降低基线K+水平，并补偿K+不足。我们的数据表明，Kir4.1通道1）在星形胶质细胞的神经元周突起中表达，2）构成星形胶质细胞Kir电导的主要部分，3）有助于调节呼吸网络中的细胞外K+。
Ongoing rhythmic neuronal activity in the ventral respiratory group (VRG) of the brain stem results in periodic changes of extracellular K+. To estimate the involvement of the weakly inwardly rectifying K+ channel Kir4.1 (KCNJ10) in extracellular K+ clearance, we examined its functional expression in astrocytes of the respiratory network. Kir4.1 was expressed in astroglial cells of the VRG, predominantly in fine astrocytic processes surrounding capillaries and in close proximity to VRG neurons. Kir4.1 expression was up-regulated during early postnatal development. The physiological role of astrocytic Kir4.1 was studied using mice with a null mutation in the Kir4.1 channel gene that were interbred with transgenic mice expressing the enhanced green fluorescent protein in their astrocytes. The membrane potential was depolarized in astrocytes of Kir4.1(-/-) mice, and Ba2+-sensitive inward K+ currents were diminished. Brain slices from Kir4.1(-/-) mice, containing the pre-Botzinger complex, which generates a respiratory rhythm, did not show any obvious differences in rhythmic bursting activity compared with wild-type controls, indicating that the lack of Kir4.1 channels alone does not impair respiratory network activity. Extracellular K+ measurements revealed that Kir4.1 channels contribute to extracellular K+ regulation. Kir4.1 channels reduce baseline K+ levels, and they compensate for the K+ undershoot. Our data indicate that Kir4.1 channels 1) are expressed in perineuronal processes of astrocytes, 2) constitute the major part of the astrocytic Kir conductance, and 3) contribute to regulation of extracellular K+ in the respiratory network.