Hyperpolarization-activated current (In) is reduced in hippocampal neurons from Gabra5-/- mice.
Hyperpolarization-activated current (In) is reduced in hippocampal neurons from Gabra5-/- mice.
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DOI：
10.1371/journal.pone.0058679
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Orser BA
中科院分区：
文献类型：
--
作者：
Bonin RP;Zurek AA;Yu J;Bayliss DA;Orser BA
γ-氨基丁酸A型（GABAA）受体表达的变化可以驱动或介导神经元兴奋性的稳态改变。最近描述了皮质神经元中含有α5亚基的GABAA（α 5 GABAA）受体（产生紧张性抑制电导）和HCN通道（产生超极化激活的阳离子电流（Ih））之间的稳态关系，其中Ih的减少伴随着α 5 GABAA受体表达的相互增加，导致树突突触功能的保留。在这里，我们报告说，在缺乏α5亚基基因（Gabra 5 −/−）的小鼠中，培养的胚胎海马锥体神经元和离体海马CA 1区神经元意外地显示出Ih电流密度降低（分别为40%和28%），与野生型（WT）小鼠的神经元相比。在培养的WT和Gabra 5 −/−神经元中，ZD-7288阻断Ih诱导的静息膜电位和膜超极化相似。相反，在一系列动作电位后测量的Gabra 5 −/−神经元的膜超极化低于WT神经元。此外，在培养的Gabra 5 −/−神经元中，对低频刺激的膜阻抗测量值更大。最后，在Gabra 5-/-小鼠的海马中，产生Ih的HCN 1蛋白的表达减少了41%。这些数据表明，紧张性GABA能抑制电导的损失，其次是Ih的代偿性减少。结果进一步表明，静息膜电位的维持优先维持在成熟和未成熟的海马神经元通过稳态的结构和bioprophically不同的阳离子和阴离子通道的共调节。
Changes in the expression of γ-aminobutyric acid type A (GABAA) receptors can either drive or mediate homeostatic alterations in neuronal excitability. A homeostatic relationship between α5 subunit-containing GABAA (α5GABAA) receptors that generate a tonic inhibitory conductance, and HCN channels that generate a hyperpolarization-activated cation current (Ih) was recently described for cortical neurons, where a reduction in Ih was accompanied by a reciprocal increase in the expression of α5GABAA receptors resulting in the preservation of dendritosomatic synaptic function. Here, we report that in mice that lack the α5 subunit gene (Gabra5−/−), cultured embryonic hippocampal pyramidal neurons and ex vivo CA1 hippocampal neurons unexpectedly exhibited a decrease in Ih current density (by 40% and 28%, respectively), compared with neurons from wild-type (WT) mice. The resting membrane potential and membrane hyperpolarization induced by blockade of Ih with ZD-7288 were similar in cultured WT and Gabra5−/− neurons. In contrast, membrane hyperpolarization measured after a train of action potentials was lower in Gabra5−/− neurons than in WT neurons. Also, membrane impedance measured in response to low frequency stimulation was greater in cultured Gabra5−/− neurons. Finally, the expression of HCN1 protein that generates Ih was reduced by 41% in the hippocampus of Gabra5−/− mice. These data indicate that loss of a tonic GABAergic inhibitory conductance was followed by a compensatory reduction in Ih. The results further suggest that the maintenance of resting membrane potential is preferentially maintained in mature and immature hippocampal neurons through the homeostatic co-regulation of structurally and biophysically distinct cation and anion channels.
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DOI：
10.1523/jneurosci.3771-09.2010
发表时间：
2010-02-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen X;Shu S;Schwartz LC;Sun C;Kapur J;Bayliss DA
通讯作者：
Bayliss DA
影响因子：
5.3
作者：
Naylor, DE;Liu, HT;Wasterlain, CG
通讯作者：
Wasterlain, CG
影响因子：
2.5
作者：
Peng, Z;Hauer, B;Houser, CR
通讯作者：
Houser, CR
影响因子：
8.8
作者：
Saab, Bechara J.;MacLean, Ashley J. B.;Orser, Beverley A.
通讯作者：
Orser, Beverley A.
影响因子：
5.5
作者：
Andrasfalvy, B. K.;Makara, J. K.;Magee, J. C.
通讯作者：
Magee, J. C.