Do glia have heart?: Expression and functional role for ether-a-go-go currents in hippocampal astrocytes
Do glia have heart?: Expression and functional role for ether-a-go-go currents in hippocampal astrocytes
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DOI：
10.1523/jneurosci.20-10-03915.2000
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发表时间：
2000-05-15
影响因子：
5.3
通讯作者：
Janigro, D
中科院分区：
文献类型：
--
作者：
Emmi, A;Wenzel, HJ;Janigro, D
钾稳态在神经元兴奋性调控中起着重要作用，细胞外钾缓冲减弱会导致神经元过度兴奋性和同步性异常。星形胶质细胞是主要参与这一过程的细胞成分。星形胶质细胞对钾的摄取至少部分是通过电压依赖的通道发生的，但涉及的确切机制尚不完全清楚。虽然大多数神经胶质细胞的记录都显示了内向整流电流(K-IR)的表达，但目前还不清楚钾的积累和释放所组成的空间缓冲是如何完全由内向的钾流量介导的。我们假设，在空间缓冲过程中，内向整流和外向整流共同作用。鉴于钾稳态(对Cs+的敏感性)的药理学特性，在神经系统中广泛表达的乙醚-a-go-go(ERG)通道家族成员可能是这一过程的一部分。我们使用电生理记录和药物操作来证明ERG型电流在培养的和原位的海马星形胶质细胞中的表达。特异性ERG阻断剂(多非利特和E 4031)抑制超极化和去极化激活的神经胶质电流，ERG阻断细胞外钾的清除，而对海马神经元的兴奋性几乎没有直接影响。免疫细胞化学分析显示，ERG蛋白主要局限于星形胶质细胞，突触前和突触后无ERG免疫反应，而突触间隙周围的胶质细胞有明显的ERG免疫反应。少突胶质细胞未显示ERG免疫反应。在血脑屏障的血管周围星形细胞末端也发现了强烈的免疫反应。基因扩增结果显示，皮质星形胶质细胞选择性表达HERG1基因，但不表达HERG2-3基因。这项研究揭示了海马区ERG通道的可能生理作用，并将ERG的激活与钾稳态的控制联系起来。
Potassium homeostasis plays an important role in the control of neuronal excitability, and diminished buffering of extracellular K results in neuronal Hyperexcitability and abnormal synchronization. Astrocytes are the cellular elements primarily involved in this process. Potassium uptake into astrocytes occurs, at least in part, through voltage-dependent channels, but the exact mechanisms involved are not fully understood. Although most glial recordings reveal expression of inward rectifier currents (K-IR), it is not clear how spatial buffering consisting of accumulation and release of potassium may be mediated by exclusively inward potassium fluxes. We hypothesized that a combination of inward and outward rectifiers cooperate in the process of spatial buffering. Given the pharmacological properties of potassium homeostasis (sensitivity to Cs+), members of the ether-a-go-go (ERG) channel family widely expressed in the nervous system could underlie part of the process. We used electrophysiological recordings and pharmacological manipulations to demonstrate the expression of ERG-type currents in cultured and in situ hippocampal astrocytes. Specific ERG blockers (dofetilide and E 4031) inhibited hyperpolarization- and depolarization-activated glial currents, and ERG blockade impaired clearance of extracellular potassium with little direct effect on hippocampal neuron excitability. Immunocytochemical analysis revealed ERG protein mostly confined to astrocytes; ERG immunoreactivity was absent in presynaptic and postsynaptic elements, but pronounced in glia surrounding the synaptic cleft. Oligodendroglia did not reveal ERG immunoreactivity. Intense immunoreactivity was also found in perivascular astrocytic end feet at the blood-brain barrier. cDNA amplification showed that cortical astrocytes selectively express HERG1, but not HERG2-3 genes. This study provides insight into a possible physiological role of hippocampal ERG channels and links activation of ERG to control of potassium homeostasis.