Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), believed to have an autoimmune etiology. MS patients showed an increased cardiovascular (CV) risk probably related to an impairment in the autonomic control of CV functions, but the underlying molecular mechanisms are not completely elucidated. Inwardly-rectifying potassium (Kir) channels play a key role in cardiac excitability by contributing to the repolarization phase of action potential and were recently identified as target of the autoantibody response in MS patients. Therefore, we investigated the role of cardiac Kir channels in the CV dysfunctions occurring in MS. Cardiac functions were evaluated by electrocardiographic recordings (ECG) in cuprizone-fed C57BL/6 mice, a classic demyelination animal model. Gene expression profiling of cardiac Kir2.2, Kir4.1 and Kir6.2 channels was performed using real-time PCR in mice. Cuprizone-induced mouse model was confirmed by immunohistochemistry analysis showing demyelination in the corpus callosum. ECG recordings from mice showed a significant decreased duration of the P wave and RR interval as well as an increase of the heart rate in cuprizone-treated mice as compared with the controls. Significant increased relative expression levels of Kcnj11 and Kcnj12, encoding for Kir6.2 and Kir2.2 channels respectively, were observed in mouse heart tissue, whereas no differences were found in mRNA levels of Kir4.1 channel as compared with controls. For the first time, these findings provided valuable insights into the potential role of Kir channels in cardiac problems associated with MS.

中文翻译：

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心脏内向整流钾通道的新作用解释了铜宗诱导的多发性硬化症小鼠模型中的自主心血管功能障碍


多发性硬化症 (MS) 是一种中枢神经系统 (CNS) 的慢性炎症性脱髓鞘和神经退行性疾病，据信具有自身免疫病因。 MS 患者心血管 (CV) 风险增加，可能与 CV 功能自主控制受损有关，但潜在的分子机制尚未完全阐明。内向整流钾 (Kir) 通道通过促进动作电位的复极相在心脏兴奋性中发挥关键作用，最近被确定为多发性硬化症患者自身抗体反应的目标。因此，我们研究了心脏 Kir 通道在 MS 发生的 CV 功能障碍中的作用。通过铜宗喂养的 C57BL/6 小鼠（一种经典的脱髓鞘动物模型）的心电图记录 (ECG) 评估心脏功能。使用实时 PCR 对小鼠心脏 Kir2.2、Kir4.1 和 Kir6.2 通道进行基因表达谱分析。铜宗诱导的小鼠模型通过免疫组织化学分析得到证实，显示胼胝体脱髓鞘。小鼠心电图记录显示，与对照组相比，铜宗治疗小鼠的 P 波持续时间和 RR 间期显着缩短，心率增加。在小鼠心脏组织中观察到分别编码 Kir6.2 和 Kir2.2 通道的 Kcnj11 和 Kcnj12 的相对表达水平显着增加，而与对照相比，Kir4.1 通道的 mRNA 水平没有发现差异。这些发现首次为人们了解 Kir 通道在 MS 相关心脏问题中的潜在作用提供了宝贵的见解。