Compartmental distribution of hyperpolarization-activated cyclic-nucleotide-gated channel 2 and hyerpolarization-activated cyclic-nucleotide-gated channel 4 in thalamic reticular and thalamocortical relay neurons
Compartmental distribution of hyperpolarization-activated cyclic-nucleotide-gated channel 2 and hyerpolarization-activated cyclic-nucleotide-gated channel 4 in thalamic reticular and thalamocortical relay neurons
复制标题
DOI：
10.1016/j.neuroscience.2006.05.034
复制
发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Goldstein, P. A.
中科院分区：
文献类型：
--
作者：
Abbas, S. Y.;Ying, S. W.;Goldstein, P. A.
超极化激活的环状核苷酸门控（HCN）通道传导单价阳离子电流，其有助于神经元的电生理学特性并调节在含有丘脑能腹基底复合体（VB）和GABA能网状丘脑核（RTN）的回路中的丘脑振荡。已经鉴定了四种不同的HCN通道同种型（HCN 1 -4），并且已经在RTN和VB中检测到HCN通道的mRNA和蛋白质，其中HCN 2和HCN 4是主要同种型。RTN和VB神经元具有不同的电生理特性，这些差异可能反映了HCN通道的可变房室分布。从C57/BI 6小鼠脑切片中获得的丘脑神经元的全细胞膜片钳记录表明，尽管I-h电流激活的时间常数非常相似，但RTN中的I-h比VB神经元中的I-h小得多。为了研究潜在通道的房室分布，我们使用荧光免疫组织化学和共聚焦显微镜对HCN 2和HCN 4表达进行了定性和定量检查。RTN神经元胞体上的HCN 2-免疫反应性（IR）比VB神经元中所见的低约10倍，而在RTN和VB神经元胞体上检测到的HCN 4-IR的程度相同。HCN 2-IR在RTN和VB没有重叠与突触素-IR，但强烈共定位与皮质素-IR，表明HCN 2不存在于轴突终末，但存在于树突棘。虽然HCN 2-IR在VB中比在RTN中更明显，但RTN中棘表达与体细胞表达的比率显著高于VB，强烈表明RTN中的HCN 2-IR主要位于索马的远端部位。相比之下，HCN 4-IR没有共定位与突触素或corneum。HCN 2-IR与HCN 4-IR在VB中的共定位大于在RTN中。结果表明，RTN和VB神经元中HCN 2通道的不同房室分布有助于这些细胞的I-H依赖性特性的深刻差异。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels conduct a monovalent cationic current, I., which contributes to the electrophysiological properties of neurons and regulates thalamic oscillations in circuits containing the glutamatergic ventrobasal complex (VB) and GABAergic reticular thalamic nucleus (RTN). Four distinct HCN channel isoforms (HCN1-4) have been identified, and mRNAs and proteins for HCN channels have been detected in the RTN and VB, with HCN2 and HCN4 being the predominant isoforms. RTN and VB neurons have distinct electrophysiological properties, and those differences may reflect variable compartmental distribution of HCN channels. Whole cell patch clamp recordings from thalamic neurons in brain slices obtained from C57/BI6 mice demonstrate that I-h is much smaller in RTN than in VB neurons although the time constants for I-h current activation are very similar. To study the compartmental distribution of the underlying channels, we performed qualitative and quantitative examination of HCN2 and HCN4 expression using fluorescent immunohistochemistry and confocal microscopy. HCN2-immunoreactivity (IR) on the somata of RTN neurons was approximately 10-fold less than that seen in VB neurons while HCN4-IR was detected on the somata of RTN and VB neurons to an equal degree. HCN2-IR in RTN and VB did not overlap with synaptophysin-IR, but strongly colocalized with cortactin-IR, indicating that HCN2 was not present in axon terminals but was present in dendritic spines. Although HCN2-IR in spines was more pronounced in VB than in RTN, the ratio of spinous to somatic expression in RTN was dramatically higher than that in VB, strongly suggesting that HCN2-IR in RTN is principally located in sites distal to the soma. In contrast, HCN4-IR did not colocalize with either synaptophysin or cortactin. The colocalization of HCN2-IR with HCN4-IR was greater in VB than in RTN. The results suggest that the distinct compartmental distribution of HCN2 channels in RTN and VB neurons contributes to the profound differences in the I-h-dependent properties of these cells. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.