Xu Jie Hua, Long Li, Tang Yong Cheng, Hu Hai Tao, Tang Feng Ru
Department of Anatomy and Histology, School of Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Hippocampus. 2007;17(3):235-51. doi: 10.1002/hipo.20263.
Calcium binding proteins are well known to be expressed by different groups of hippocampal interneurons; however, whether voltage-dependent calcium channels (Ca(v)) are also localized in these neurons, changed during and after status epilepticus (SE), and involved in epileptic activity have not been reported. In the present study, we showed the colocalization of three subtypes of voltage-gated calcium channels (Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1) with different calcium binding proteins such as calbindin (CB), calretinin (CR), and parvalbumin (PV). At early stages during and after pilocarpine-induced status epilepticus (PISE), significant changes of expression of Ca(v)1.2, Ca(v)1.3 (L-type), and Ca(v)2.1 (P/Q-type) were found in different groups of hippocampal neurons. Induced expression of Ca(v)1.3 or Ca(v)2.1 in reactive astrocytes was shown at 1 week and 2 months after PISE. At the latter time point, higher percentages of colocalization of PV and Ca(v)1.2, CB, or PV and Ca(v)1.3 or Ca(v)2.1, lower percentages of CR and Ca(v)1.3 or Ca(v)2.1 immunoposivie neurons were observed in gliotic CA1 area. We therefore conclude that voltage-gated calcium channels are expressed by different groups of hippocampal interneurons in the mouse. At acute stages during and after PISE, up- or down-regulation of Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1 in functionally different groups of interneurons in CA1 area may be related to the changes of their plasticity. Up-regulation of Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1 in granule cells may be directly related to the occurrence of SE. The induced expression of Ca(v)1.3 or Ca(v)2.1 in reactive astrocytes at 1 week and 2 months after PISE suggests that Ca(v)1.3 or Ca(v)2.1-related calcium signaling in reactive astrocytes may be involved in initiation, maintenance or spread of seizure activity. In gliotic CA1 area at chronic stage (i.e., 2 months after PISE), the occurrence of higher percentages of colocalization of PV and Ca(v)1.2, CB, or PV and Ca(v)1.3 or Ca(v)2.1, lower percentages of CR and Ca(v)1.3 or Ca(v)2.1 immunopositive neurons may suggest that such colocalizations may be linked to the survival or loss of particular group of hippocampal neurons.
众所周知，钙结合蛋白由不同组的海马中间神经元表达；然而，电压依赖性钙通道（Ca(v)）是否也定位于这些神经元中、在癫痫持续状态（SE）期间及之后是否发生变化以及是否参与癫痫活动，目前尚无报道。在本研究中，我们展示了三种电压门控钙通道亚型（Ca(v)1.2、Ca(v)1.3或Ca(v)2.1）与不同的钙结合蛋白如钙结合蛋白（CB）、钙视网膜蛋白（CR）和小白蛋白（PV）的共定位。在毛果芸香碱诱导的癫痫持续状态（PISE）期间及之后的早期阶段，在不同组的海马神经元中发现Ca(v)1.2、Ca(v)1.3（L型）和Ca(v)2.1（P/Q型）表达有显著变化。在PISE后1周和2个月时，在反应性星形胶质细胞中显示出Ca(v)1.3或Ca(v)2.1的诱导表达。在后期时间点，在胶质化的CA1区域观察到PV与Ca(v)1.2、CB，或PV与Ca(v)1.3或Ca(v)2.1共定位的神经元百分比更高，而CR与Ca(v)1.3或Ca(v)2.1免疫阳性神经元的百分比更低。因此，我们得出结论，电压门控钙通道在小鼠不同组的海马中间神经元中表达。在PISE期间及之后的急性期，CA1区域功能不同的中间神经元组中Ca(v)1.2、Ca(v)1.3或Ca(v)2.1的上调或下调可能与其可塑性变化有关。颗粒细胞中Ca(v)1.2、Ca(v)1.3或Ca(v)2.1的上调可能与SE的发生直接相关。PISE后1周和2个月时反应性星形胶质细胞中Ca(v)1.3或Ca(v)2.1的诱导表达表明，反应性星形胶质细胞中与Ca(v)1.3或Ca(v)2.1相关的钙信号可能参与癫痫活动的起始、维持或传播。在慢性期（即PISE后2个月）的胶质化CA1区域，PV与Ca(v)1.2、CB，或PV与Ca(v)1.3或Ca(v)2.1共定位的神经元百分比更高，而CR与Ca(v)1.3或Ca(v)2.1免疫阳性神经元的百分比更低，这可能表明这种共定位可能与特定组海马神经元的存活或丧失有关。
