Role of HCN Channels in Neuronal Hyperexcitability after Subarachnoid Hemorrhage in Rats
Role of HCN Channels in Neuronal Hyperexcitability after Subarachnoid Hemorrhage in Rats
复制标题
HCN通道在大鼠蛛网膜下腔出血后神经元过度兴奋中的作用
DOI：
10.1523/jneurosci.5143-11.2012
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发表时间：
2012-02-29
影响因子：
5.3
通讯作者：
Feng, Hua
中科院分区：
文献类型：
--
作者：
Li, Bo;Luo, Chunxia;Feng, Hua
蛛网膜下腔出血（SAH）后早期脑损伤的原因是离子稳态的破坏和神经元的过度兴奋。超极化激活/环核苷酸（HCN）门控通道在调节海马CA 1区和新皮层神经元兴奋性中起着重要作用，在这些区域更容易引起异常神经元活动。本研究旨在探讨实验性SAH后HCN通道与超神经元活动的相互作用。用大鼠脑片全细胞记录的结果表明：（1）含血红蛋白（Hb）的人工脑脊液灌流可引起海马CA 1区锥体神经元的兴奋性增高，并抑制HCN电流;（2）一氧化氮/精胺（NO/Sp）抑制海马CA 1区锥体神经元的兴奋性，并增强HCN电流;一氧化氮合酶的抑制剂，减少HCN电流;（3）血红蛋白对HCN电流的抑制作用被逆转的应用NO/SP，这也降低神经元的过度兴奋性;相反，l-NNA增强血红蛋白对HCN电流的抑制作用。此外，Hb灌流还可减少一氧化氮的产生，并降低CA 1区HCN 1亚基的表达。SAH模型大鼠海马CA 1区HCN 1 mRNA和蛋白表达在SAH后24 h均降低，72 h表达更明显。这些观察结果表明，减少HCN通道的表达后，SAH和血红蛋白减少HCN电流在海马CA 1锥体神经元。血红蛋白对HCN通道的抑制可能是SAH后神经元兴奋性增高的一条新途径。
Disruption of ionic homeostasis and neuronal hyperexcitability contribute to early brain injury after subarachnoid hemorrhage (SAH). The hyperpolarization-activated/cyclic nucleotide (HCN)-gated channels play critical role in the regulation of neuronal excitability in hippocampus CA1 region and neocortex, in which the abnormal neuronal activities are more readily provoked. This study was to investigate the interactions between HCN channels and hyperneuronal activity after experimental SAH. The present results from whole-cell recordings in rat brain slices indicated that (1) perfusion of hemoglobin (Hb)-containing artificial CSF produced neuronal hyperexcitability and inhibited HCN currents in CA1 pyramidal neurons, (2) nitric oxide/Spermine (NO/Sp), a controlled releaser of nitric oxide, attenuated neuronal excitability and enhanced HCN currents in CA1 pyramidal neurons, while l-nitroarginine (l-NNA), an inhibitor of nitric oxide synthase, reduced the HCN currents; and (3) the inhibitory action of Hb on HCN currents was reversed by application of NO/Sp, which also reduced neuronal hyperexcitability; conversely, l-NNA enhanced inhibitory action of Hb on HCN currents. Additionally, Hb perfusion scavenged the production of nitric oxide and decreased the expression of HCN1 subunits in CA1 region. In the rat SAH model, the expression of HCN1, both at mRNA and protein level, decreased in hippocampus CA1 region at 24 h and more pronounced at 72 h after SAH. These observations demonstrated a reduction of HCN channels expression after SAH and Hb reduced HCN currents in hippocampus CA1 pyramidal neurons. Inhibition of HCN channels by Hb may be a novel pathway for inducing the hyperneuronal excitability after SAH.