Kv4.2 knockout mice demonstrate increased susceptibility to convulsant stimulation
Kv4.2 knockout mice demonstrate increased susceptibility to convulsant stimulation
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DOI：
10.1111/j.1528-1167.2009.02086.x
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发表时间：
2009-07-01
期刊：
影响因子：
5.6
通讯作者：
Anderson, Anne E.
中科院分区：
文献类型：
--
作者：
Barnwell, L. Forbes S.;Lugo, Joaquin N.;Anderson, Anne E.
目的：Kv4.2亚基参与海马CA1区锥体细胞树突上表达瞬时A型钾电流的通道的成孔区。在这里，A电流在信号处理和突触整合中起着重要作用。Kv4.2基因敲除小鼠表现出在CA1区树突中A电流的几乎消除，在该区域产生增加的兴奋性。在这些研究中，我们评估了年轻的成年Kv4.2基因敲除小鼠的自发性癫痫发作和惊厥刺激的反应，在整个动物在体内和海马slices in vitro.Methods：脑电图电极植入Kv4.2基因敲除和野生型小鼠自发性行为和脑电图癫痫发作。Kv4.2基因敲除小鼠和野生型小鼠在腹腔注射红藻氨酸后评估癫痫发作和癫痫持续状态发作的潜伏期。结果：Kv4.2基因敲除小鼠和野生型小鼠海马脑片均未出现自发性行为或电描记性癫痫发作。红藻氨酸后，Kv4.2敲除小鼠表现出减少癫痫发作和癫痫持续状态潜伏期以及增加死亡率相比，野生型同窝仔。背景菌株改变了Kv4.2基因敲除小鼠的癫痫发作易感性表型。在响应荷包牡丹碱，从Kv4.2基因敲除小鼠的切片表现出增加癫痫样爆裂在CA1区相比，野生型littermates.Discussion：这些研究表明，Kv4.2通道的损失与增强的敏感性惊厥刺激，支持的概念，Kv4.2缺陷可能有助于异常的网络兴奋性和调节癫痫发作阈值。
P>Purpose:Kv4.2 subunits contribute to the pore-forming region of channels that express a transient, A-type K+ current (A-current) in hippocampal CA1 pyramidal cell dendrites. Here, the A-current plays an important role in signal processing and synaptic integration. Kv4.2 knockout mice show a near elimination of the A-current in area CA1 dendrites, producing increased excitability in this region. In these studies, we evaluated young adult Kv4.2 knockout mice for spontaneous seizures and the response to convulsant stimulation in the whole animal in vivo and in hippocampal slices in vitro.Methods:Electroencephalogram electrode-implanted Kv4.2 knockout and wild-type mice were observed for spontaneous behavioral and electrographic seizures. The latency to seizure and status epilepticus onset in Kv4.2 knockout and wild-type mice was assessed following intraperitoneal injection of kainate. Extracellular field potential recordings were performed in hippocampal slices from Kv4.2 knockout and wild-type mice following the bath application of bicuculline.Results:No spontaneous behavioral or electrographic seizures were observed in Kv4.2 knockout mice. Following kainate, Kv4.2 knockout mice demonstrated a decreased seizure and status epilepticus latency as well as increased mortality compared to wild-type littermates. The background strain modified the seizure susceptibility phenotype in Kv4.2 knockout mice. In response to bicuculline, slices from Kv4.2 knockout mice exhibited an increase in epileptiform bursting in area CA1 as compared to wild-type littermates.Discussion:These studies show that loss of Kv4.2 channels is associated with enhanced susceptibility to convulsant stimulation, supporting the concept that Kv4.2 deficiency may contribute to aberrant network excitability and regulate seizure threshold.