Potassium channel activity and glutamate uptake are impaired in astrocytes of seizure-susceptible DBA/2 mice.
Potassium channel activity and glutamate uptake are impaired in astrocytes of seizure-susceptible DBA/2 mice.
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DOI：
10.1111/j.1528-1167.2010.02592.x
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发表时间：
2010-09
期刊：
影响因子：
5.6
通讯作者：
Eaton MJ
中科院分区：
文献类型：
--
作者：
Inyushin M;Kucheryavykh LY;Kucheryavykh YV;Nichols CG;Buono RJ;Ferraro TN;Skatchkov SN;Eaton MJ
KCNJ10 编码主要存在于大脑内神经胶质细胞中的内向整流钾 (Kir) 通道 Kir4.1 亚基。神经胶质细胞中这些通道的基因失活会损害细胞外 K+ 和谷氨酸清除率并产生癫痫表型。在小鼠和人类中，KCNJ10 基因的多态性和突变都与癫痫易感性相关。本研究的目的是确定癫痫抗性 C57BL/6 (B6) 和癫痫易感 DBA/2 (D2) 小鼠的星形胶质细胞之间的 Kir 通道活性以及钾和谷氨酸缓冲能力是否存在差异，这些差异与 KCNJ10 遗传多态性导致的 K+ 通道活性改变一致。使用培养的星形胶质细胞和海马脑切片以及全细胞膜片钳，我们确定了 B6 和 D2 小鼠星形胶质细胞的电生理特性，特别是 K+ 电导。使用比色测定法，我们测定了 B6 和 D2 星形胶质细胞的谷氨酸清除能力。 B6 星形胶质细胞产生的对钡敏感的 Kir 电流明显大于 D2 星形胶质细胞产生的电流。此外，相对于 B6 星形胶质细胞的缓冲，D2 皮质星形胶质细胞的钾和谷氨酸缓冲受到损害。总之，癫痫易感 D2 小鼠和癫痫抗性 B6 小鼠的 Kir4.1 通道活性不同。 D2 小鼠星形胶质细胞中 Kir4.1 通道活性的降低与钾和谷氨酸缓冲缺陷有关。这些缺陷可能部分解释了 D2 小鼠癫痫发作阈值相对较低的原因。
KCNJ10 encodes subunits of inward rectifying potassium (Kir) channel Kir4.1 found predominantly in glial cells within the brain. Genetic inactivation of these channels in glia impairs extracellular K+ and glutamate clearance and produces a seizure phenotype. In both mice and humans, polymorphisms and mutations in the KCNJ10 gene have been associated with seizure susceptibility. The purpose of the present study was to determine whether there are differences in Kir channel activity and potassium and glutamate buffering capabilities between astrocytes from seizure resistant C57BL/6 (B6) and seizure susceptible DBA/2 (D2) mice that are consistent with an altered K+ channel activity as a result of genetic polymorphism of KCNJ10. Using cultured astrocytes and hippocampal brain slices together with whole-cell patch-clamp, we determined the electrophysiological properties, particularly K+ conductances, of B6 and D2 mouse astrocytes. Using a colorimetric assay, we determined glutamate clearance capacity by B6 and D2 astrocytes. Barium-sensitive Kir currents elicited from B6 astrocytes are substantially larger than those elicited from D2 astrocytes. In addition, potassium and glutamate buffering by D2 cortical astrocytes is impaired, relative to buffering by B6 astrocytes. In summary, the activity of Kir4.1 channels differs between seizure susceptible D2 and seizure resistant B6 mice. Reduced activity of Kir4.1 channels in astrocytes of D2 mice is associated with deficits in potassium and glutamate buffering. These deficits may, in part, explain the relatively low seizure threshold of D2 mice.
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影响因子：
4.8
作者：
Connors, NC;Adams, ME;Kofuji, P
通讯作者：
Kofuji, P
影响因子：
5.3
作者：
Djukic, Biljana;Casper, Kristen B.;McCarthy, Ken D.
通讯作者：
McCarthy, Ken D.
影响因子：
3.4
作者：
Hinterkeuser, S;Schröder, W;Steinhäuser, C
通讯作者：
Steinhäuser, C
影响因子：
2.5
作者：
Neusch, C;Papadopoulos, N;Hülsmann, S
通讯作者：
Hülsmann, S
DOI：
10.1152/ajpcell.2001.281.3.c922
发表时间：
2001-09-01
影响因子：
5.5
作者：
Higashi, K;Fujita, A;Kurachi, Y
通讯作者：
Kurachi, Y