Dept. of Neuroscience, Univ. of Minnesota, 321 Church St., Minneapolis, MN 55455, USA.
J Neurophysiol. 2012 Jan;107(1):103-13. doi: 10.1152/jn.00583.2011. Epub 2011 Oct 12.
In this study, we examined the contribution of a low-threshold calcium current [I(Ca(T))] to locomotor-related activity in the neonatal mouse. Specifically, the role of I(Ca(T)) was studied during chemically induced, locomotor-like activity in the isolated whole cord and in a genetically distinct population of ventromedial spinal interneurons marked by the homeobox gene Hb9. In isolated whole spinal cords, cycle frequency was decreased in the presence of low-threshold calcium channel blockers, which suggests a role for I(Ca(T)) in the network that produces rhythmic, locomotor-like activity. Additionally, we used Hb9 interneurons as a model to study the cellular responses to application of low-threshold calcium channel blockers. In transverse slice preparations from transgenic Hb9::enhanced green fluorescent protein neonatal mice, N-methyl-d-aspartate-induced membrane potential oscillations in identified Hb9 interneurons also slowed in frequency with application of nickel when fast, spike-mediated, synaptic transmission was blocked with TTX. Voltage-clamp and immunolabeling experiments confirmed expression of I(Ca(T)) and channels, respectively, in Hb9 interneurons located in the ventromedial spinal cord. Taken together, these results provide support that T-type calcium currents play an important role in network-wide rhythm generation during chemically evoked, fictive locomotor activity.
在这项研究中，我们研究了低阈值钙电流 [I(Ca(T))] 对新生小鼠运动相关活动的贡献。具体来说，我们研究了在整个脊髓离体和由同源盒基因 Hb9 标记的特定的腹侧脊髓中间神经元中化学诱导的、类似运动的活动期间 I(Ca(T)) 的作用。在整个脊髓离体中，低阈值钙通道阻滞剂的存在降低了周期频率，这表明 I(Ca(T)) 在产生节律性、类似运动的活动的网络中起作用。此外，我们使用 Hb9 中间神经元作为模型来研究对低阈值钙通道阻滞剂应用的细胞反应。在转 Hb9::增强型绿色荧光蛋白新生小鼠的横切片制备中，当快速、尖峰介导的突触传递被 TTX 阻断时，N-甲基-D-天冬氨酸诱导的已鉴定 Hb9 中间神经元的膜电位振荡的频率也随着镍的应用而减慢。电压钳和免疫标记实验分别证实了位于腹侧脊髓中的 Hb9 中间神经元中 I(Ca(T)) 和通道的表达。综上所述，这些结果支持 T 型钙电流在化学诱发的、虚拟运动活动期间的全网络节律产生中发挥重要作用。
