Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA 22908, USA.
Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA 22908, USA; Neuroscience Graduate Program, University of Virginia Health System, Charlottesville, VA 22908, USA.
Epilepsy Res. 2019 Aug;154:132-138. doi: 10.1016/j.eplepsyres.2019.05.006. Epub 2019 May 18.
Temporal lobe epilepsy (TLE) is a form of adult epilepsy involving the entorhinal cortex (EC). Layer II neurons of the medial EC (mEC) are spared and become hyperexcitable in TLE. Studies have suggested a role for T-type calcium channels (T-type Ca channels) in facilitating increases in neuronal activity associated with TLE within the hippocampus. We sought to determine if T-type Ca channels play a role in facilitating neuronal hyperexcitability of layer II mEC stellate neurons in TLE. TLE was induced in rats by electrical stimulation of the hippocampus to induce status epilepticus (SE). Brain slices were prepared from rats exhibiting spontaneous seizures and compared with age-matched control rats. Action potentials (APs) were evoked either by current injection steps or via presynaptic stimulation of mEC deep layers. The selective T-type Ca channel antagonist, TTA-P2 (1 μM), was applied to determine the role of T-type Ca channels in maintaining neuronal excitability. Quantitative PCR techniques were used to assess T-type Ca channel isoform mRNA levels within the mEC layer II. TLE mEC layer II stellate neurons were hyperexcitable compared to control neurons, evoking a higher frequency of APs and generating bursts of APs when synaptically stimulated. TTA-P2 (1 μM) reduced firing frequencies in TLE and control neurons and reduced AP burst firing in TLE stellate neurons. TTA-P2 had little effect on synaptically evoked AP's in control neurons. TTA-P2 also inhibited rebound APs evoked in TLE neurons to a greater degree than in control neurons. TLE tissue had almost a 3-fold increase in Ca3.1 mRNA compared to controls. Ca3.2 or Ca3.3 levels were unchanged. These findings support a role for T-type Ca channel in establishing neuronal hyperexcitability of mEC layer II stellate neurons in TLE. Increased expression of Ca3.1 may be important for establishing neuronal hyperexcitability of mEC layer II neurons in TLE.
颞叶癫痫（TLE）是一种涉及内嗅皮层（EC）的成人癫痫形式。内侧 EC（mEC）的 II 层神经元在 TLE 中免受损伤并变得过度兴奋。研究表明 T 型钙通道（T 型钙通道）在促进与 TLE 相关的海马神经元活动增加方面发挥作用。我们试图确定 T 型钙通道是否在促进 TLE 中 mEC 星状神经元 II 层神经元的过度兴奋中发挥作用。通过电刺激海马诱导癫痫持续状态（SE）来诱导 TLE 在大鼠中。从表现出自发性发作的大鼠中制备脑切片，并与年龄匹配的对照大鼠进行比较。通过电流注入步骤或通过 mEC 深层的突触前刺激来诱发动作电位（AP）。应用选择性 T 型钙通道拮抗剂 TTA-P2（1 μM）来确定 T 型钙通道在维持神经元兴奋性中的作用。使用定量 PCR 技术评估 mEC 层 II 中的 T 型钙通道同工型 mRNA 水平。与对照神经元相比，TLE mEC 层 II 星状神经元过度兴奋，在突触刺激时引发更高频率的 AP 并产生 AP 爆发。TTA-P2（1 μM）降低了 TLE 和对照神经元的放电频率，并降低了 TLE 星状神经元的 AP 爆发放电。TTA-P2 对对照神经元突触诱发的 AP 几乎没有影响。TTA-P2 还抑制了 TLE 神经元中比对照神经元更大程度的反弹 AP。与对照相比，TLE 组织中的 Ca3.1 mRNA 增加了近 3 倍。Ca3.2 或 Ca3.3 水平没有变化。这些发现支持 T 型钙通道在 TLE 中建立 mEC 层 II 星状神经元神经元过度兴奋中的作用。Ca3.1 的表达增加可能对于建立 TLE 中 mEC 层 II 神经元的神经元过度兴奋很重要。
