Dufour Martial A, Woodhouse Adele, Goaillard Jean-Marc
INSERM, UMR_S 1072, 13015, Marseille, France; Aix-Marseille Université, UNIS, 13015, Marseille, France.
J Neurosci Res. 2014 Aug;92(8):981-99. doi: 10.1002/jnr.23382. Epub 2014 Apr 10.
Dopaminergic neurons of the substantia nigra pars compacta (SNc) are involved in the control of movement, sleep, reward, learning, and nervous system disorders and disease. To date, a thorough characterization of the ion channel phenotype of this important neuronal population is lacking. Using immunohistochemistry, we analyzed the somatodendritic expression of voltage-gated ion channel subunits that are involved in pacemaking activity in SNc dopaminergic neurons in 6-, 21-, and 40-day-old rats. Our results demonstrate that the same complement of somatodendritic ion channels is present in SNc dopaminergic neurons from P6 to P40. The major developmental changes were an increase in the dendritic range of the immunolabeling for the HCN, T-type calcium, Kv4.3, delayed rectifier, and SK channels. Our study sheds light on the ion channel subunits that contribute to the somatodendritic delayed rectifier (Kv1.3, Kv2.1, Kv3.2, Kv3.3), A-type (Kv4.3) and calcium-activated SK (SK1, SK2, SK3) potassium currents, IH (mainly HCN2, HCN4), and the L- (Cav1.2, Cav1.3) and T-type (mainly Cav3.1, Cav3.3) calcium currents in SNc dopaminergic neurons. Finally, no robust differences in voltage-gated ion channel immunolabeling were observed across the population of SNc dopaminergic neurons for each age examined, suggesting that differing levels of individual ion channels are unlikely to distinguish between specific subpopulations of SNc dopaminergic neurons. This is significant in light of previous studies suggesting that age- or region-associated variations in the expression profile of voltage-gated ion channels in SNc dopaminergic neurons may underlie their vulnerability to dysfunction and disease.
黑质致密部（SNc）的多巴胺能神经元参与运动、睡眠、奖赏、学习以及神经系统疾病的控制。迄今为止，尚缺乏对这一重要神经元群体离子通道表型的全面描述。我们采用免疫组织化学方法，分析了6日龄、21日龄和40日龄大鼠SNc多巴胺能神经元中参与起搏活动的电压门控离子通道亚单位的树突-胞体表达。我们的结果表明，从出生后第（P）6天到P40天，SNc多巴胺能神经元中存在相同的树突-胞体离子通道组合。主要的发育变化是超极化激活的环核苷酸门控（HCN）通道、T型钙通道、Kv4.3通道、延迟整流钾通道和小电导钙激活钾（SK）通道免疫标记的树突范围增加。我们的研究揭示了对SNc多巴胺能神经元的树突-胞体延迟整流钾电流（Kv1.3、Kv2.1、Kv3.2、Kv3.3）、A 型钾电流（Kv4.3）和钙激活SK钾电流（SK1、SK2、SK3）、超极化激活电流（IH，主要是HCN2、HCN4）以及L型钙电流（Cav1.2、Cav1.3）和T型钙电流（主要是Cav3.1、Cav3.3）有贡献的离子通道亚单位。最后，在所检查的每个年龄组的SNc多巴胺能神经元群体中，未观察到电压门控离子通道免疫标记有明显差异，这表明不同水平的单个离子通道不太可能区分SNc多巴胺能神经元的特定亚群。鉴于之前的研究表明，SNc多巴胺能神经元中电压门控离子通道表达谱的年龄或区域相关变化可能是其功能障碍和疾病易感性的基础，这一结果具有重要意义。
