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在生理和模拟缺血条件下大鼠海马切片中海马星形细胞的电偶联。

Electrical coupling of astrocytes in rat hippocampal slices under physiological and simulated ischemic conditions.

机构信息

Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

出版信息

Glia. 2010 Mar;58(4):481-93. doi: 10.1002/glia.20939.

DOI:10.1002/glia.20939
PMID:19795502
Abstract

Mammalian protoplasmic astrocytes are extensively coupled through gap junction channels but the biophysical properties of these channels under physiological and ischemic conditions in situ are not well defined. Using confocal morphometric analysis of biocytin-filled astrocytic syncytia in rat hippocampal CA1 stratum radiatum we found that each astrocyte directly couples, on average, to 11 other astrocytes with a mean interastrocytic distance of 45 microm. Voltage-independent and bidirectional transjunctional currents were always measured between directly coupled astrocyte pairs in dual voltage-clamp recordings, but never from astrocyte-NG2 glia or astrocyte-interneuron pairs. The electrical coupling ratio varied considerably among astrocytes in developing postnatal day 14 rats (P14, 0.5-12.4%, mean = 3.6%), but became more constant in young adult P21 rats (0.18-3.9%, mean = 1.6%), and the coupling ratio declined exponentially with increasing pair distance. Electrical coupling was not affected by short-term oxygen-glucose deprivation (OGD) treatment, but showed delayed inhibition in an acidic extracellular pH of 6.4. Combination of acidic pH (6.4) and OGD, a condition that better represents cerebral ischemia in vivo, accelerated the inhibition of electrical coupling. Our results show that, under physiological conditions, 20.7-24.2% of K(+) induced currents can travel from any astrocytic soma in CA1 stratum radiatum to the gap junctions of the nearest neighbor astrocytes, but this should be severely inhibited as a consequence of the OGD and acidosis seen in the ischemic brain.

摘要

哺乳动物原代细胞质星形细胞通过缝隙连接通道广泛偶联,但在生理和缺血条件下这些通道的生物物理特性在原位尚未很好地确定。我们使用大鼠海马 CA1 放射状层中生物胞素填充的星形细胞合胞体的共聚焦形态计量分析发现,每个星形细胞平均直接与 11 个其他星形细胞偶联,平均星形细胞间距离为 45 微米。在双电压钳记录中,始终在直接偶联的星形细胞对之间测量电压独立和双向跨连接电流,但从未从星形细胞-NG2 神经胶质或星形细胞-中间神经元对中测量到。在发育中的出生后第 14 天大鼠 (P14,0.5-12.4%,平均值 = 3.6%) 中,电偶联比率在星形细胞之间变化很大,但在年轻的成年大鼠 (P21,0.18-3.9%,平均值 = 1.6%) 中变得更稳定,并且偶联比率随偶联对距离的增加呈指数下降。电偶联不受短期氧葡萄糖剥夺 (OGD) 处理的影响,但在 pH 值为 6.4 的酸性细胞外环境中表现出延迟抑制。酸性 pH (6.4) 和 OGD 的组合,更能代表体内脑缺血,加速了电偶联的抑制。我们的结果表明,在生理条件下,20.7-24.2%的 K(+)诱导电流可以从 CA1 放射状层中的任何星形细胞体传播到最近的星形细胞的缝隙连接,但由于缺血性脑内的 OGD 和酸中毒,这种传播应该会受到严重抑制。

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