Physiological function of Na pumpα3 subunit gene and involvement in pathophysiology of dystonia parkinsonism.

肌张力障碍的特征是激动剂和拮抗剂肌肉同时过度不自主和长时间的收缩。肌张力障碍的一种遗传形式DYT12是由Na泵α3亚型基因（ATP1A3）的功能突变丧失引起的。为了深入了解DYT12的分子病因，我们生成并分析了敲除杂合小鼠（Atp1a3^<+/->）。Atp1a3^<+/->小鼠对盐酸盐诱导的肌张力障碍的敏感性高于野生型（WT）。电生理研究显示浦肯野细胞对小脑抑制性突触Atp1a3^<+/->的反应增强。我们的研究结果揭示了Atp1a3在抑制性突触中的作用，以及它可能参与DYT12肌张力障碍症状的表达。

Dystonia is characterized by excessive involuntary and prolonged simultaneous contractions of both agonist and antagonist muscles. One hereditary form of dystonia, DYT12, is caused by loss of function mutations of the gene forα3 isoform of Na pump(ATP1A3). To provide insight into the molecular etiology of DYT12, we generated and analyzed knockout heterozygous mice(Atp1a3^<+/->). Atp1a3^<+/-> mice showed increased sensitivity to kainate-induced dystonia than wild-type littermates(WT). Electrophysiological studies showed enhanced response of Purkinje cells in Atp1a3^<+/-> at cerebellar inhibitory synapses. Our results shed light on the role of Atp1a3 in inhibitory synapse, and its potential involvement in the expression of dystonia symptoms of DYT12.