Electrophysiological behavior of neonatal astrocytes in hippocampal stratum radiatum.
Electrophysiological behavior of neonatal astrocytes in hippocampal stratum radiatum.
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DOI：
10.1186/s13041-016-0213-7
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发表时间：
2016-03-22
期刊：
影响因子：
3.6
通讯作者：
Zhou M
中科院分区：
文献类型：
--
作者：
Zhong S;Du Y;Kiyoshi CM;Ma B;Alford CC;Wang Q;Yang Y;Liu X;Zhou M
新生星形胶质细胞起源多样，在整个发育过程中基因表达、形态分化和合胞体网络发生了巨大变化。新生星形胶质细胞在神经元回路建立中也发挥多方面的作用。然而，新生星形胶质细胞与成人大脑中的对应物的差异程度仍然未知。基于ALDH 1 L1-eGFP表达或磺酰罗丹明101染色，出生后1-3天的新生星形胶质细胞可以在海马放射层中可靠地鉴定。由于电压门控外向瞬时K+（IKa）、延迟整流K+（IKd）和内向K+（IKin）电导的复杂表达，它们表现出比成熟星形胶质细胞（-80 mV）更负的静息膜电位（VM）（-85 mV）和整流全细胞电流曲线。与NG 2胶质细胞不同，新生星形胶质细胞未检测到去极化诱导的内向钠电流（INa）。在野生型和TWIK-1/TREK-1双基因敲除星形胶质细胞中，当内向整流Kir4.1被100 μM Ba 2+抑制时，保留了−69 mV的准生理VM，表明表达了额外的泄漏K+通道，但尚不清楚。在双膜片记录中，在74%（14/19对）的新生星形胶质细胞中检测到电耦合，耦合系数变化很大。逐渐增加的间隙连接耦合掩盖了整流K+电导，占越来越多的线性电压-电流关系被动星形胶质细胞（PA）。通过100 μM甲氨酰胺酸抑制间隙连接，可显著降低膜电导，并将所有新生PA转化为整流性星形胶质细胞。与成人星形胶质细胞相比，新生星形胶质细胞中渗漏K+电导的低密度表达对应于约50%的K+摄取能力。新生星形胶质细胞主要表达各种整流K+电导，形成离散的细胞-细胞间隙连接偶联，并且缺乏K+稳态能力。
Neonatal astrocytes are diverse in origin, and undergo dramatic change in gene expression, morphological differentiation and syncytial networking throughout development. Neonatal astrocytes also play multifaceted roles in neuronal circuitry establishment. However, the extent to which neonatal astrocytes differ from their counterparts in the adult brain remains unknown. Based on ALDH1L1-eGFP expression or sulforhodamine 101 staining, neonatal astrocytes at postnatal day 1–3 can be reliably identified in hippocampal stratum radiatum. They exhibit a more negative resting membrane potential (VM), −85 mV, than mature astrocytes, −80 mV and a variably rectifying whole-cell current profile due to complex expression of voltage-gated outward transient K+ (IKa), delayed rectifying K+ (IKd) and inward K+ (IKin) conductances. Differing from NG2 glia, depolarization-induced inward Na+ currents (INa) could not be detected in neonatal astrocytes. A quasi-physiological VM of −69 mV was retained when inwardly rectifying Kir4.1 was inhibited by 100 μM Ba2+ in both wild type and TWIK-1/TREK-1 double gene knockout astrocytes, indicating expression of additional leak K+ channels yet unknown. In dual patch recording, electrical coupling was detected in 74 % (14/19 pairs) of neonatal astrocytes with largely variable coupling coefficients. The increasing gap junction coupling progressively masked the rectifying K+ conductances to account for an increasing number of linear voltage-to-current relationship passive astrocytes (PAs). Gap junction inhibition, by 100 μM meclofenamic acid, substantially reduced membrane conductance and converted all the neonatal PAs to variably rectifying astrocytes. The low density expression of leak K+ conductance in neonatal astrocytes corresponded to a ~50 % less K+ uptake capacity compared to adult astrocytes. Neonatal astrocytes predominantly express a variety of rectifying K+ conductances, form discrete cell-to-cell gap junction coupling and are deficient in K+ homeostatic capacity.