电压门控性钾、钙、钠离子通道的结构及分类

电压门控性钾、钙和钠离子通道在生命科学研究领域中受到越来越多的关注。最近，国际芍理学联合会(IUPHAR)及美国药理学和临床治疗学会(ASPET)联合制定了新的电压门控性离子通道置家族分类方法，本文将对其中的电压门控性钾、钙和钠离子通道进行介绍。     

莫旺综合征误诊为抑郁症1例

莫旺综合征(Morvan's syndrome)是由获得性神经性肌强直(肌肉不自主抽搐以及肌肉僵硬),肌无力,严重失眠,过度出汗和由脑病引起的意识模糊、幻觉和认知功能障碍组成的综合征,是一种罕见的自身免疫性脑炎,伴有抗电压门控钾通道(voltage-gated potassium channel,VGKC)抗体异常,抗VGKC抗体包括抗接触蛋白相关蛋白2(contactin-associated protein-like 2,CASPR2)抗体、抗富亮氨酸胶质瘤失活蛋白1(leucin-rich glioma-inactivated 1 protein,LGI-1)抗体及其他抗体[1-2]。本病症状形式多样,易被临床医生忽视或误诊为抑郁障碍、睡眠障碍、代谢性疾病等,早期诊断与免疫治疗有助于改善预后。目前国内对本病研究较少。本文报道1例误诊为抑郁症的莫旺综合征患者临床资料及诊治经过,结合文献对该病进行复习,以提高临床医生对莫旺综合征的认识。     

莫旺综合征:1例报道及文献复习

本文报道了1例莫旺综合征(Morvan's syndrome)成年患者的临床诊治过程。该患者男性,75岁,主要临床表现为肢体肌肉颤搐和无力、多汗、睡眠障碍、幻视等;辅助检查提示胸腺恶性病变可能;外周血抗电压门控钾通道(voltage-gated potassmm channel,VGKC)抗体等免疫学指标异常。在明确诊断为莫旺综合征后,该例患者接受了对症支持治疗,症状得以部分缓解。     

第三讲 电压门控离子通道

在所有可兴奋细胞的细胞膜上都有许多蛋白通道。这些通道打开时 ,允许各种离子通过。其中 ,有些通道的打开由跨膜电压控制 ,称为电压门控离子通道。它们的特点是对某一种离子有特别高的通透性 ,根据离子通透的选择性可鉴别与区分离子通道。神经细胞中第一个被识别的电压门控离子通道是钠通道 (VDSC)和钾通道 (VDKC) ,它们决定着膜动作电位的变化。 Alan Hidgkin和 Andrew Huxley应用电压钳 (Voltageclamping)并结合药理学技术在枪鸟贼轴突上首先研究了钠通道和钾通道 ,证明动作电位由早期流入细胞的钠电流和晚期流出的钾电流组成。钠…     

电压门控钾离子通道复合物抗体相关临床综合征合并伴胸腺瘤的重症肌无力患者2例及文献复习

目的探讨电压门控钾离子通道复合物(VGKCc)抗体相关临床综合征合并伴胸腺瘤的重症肌无力(MG)患者的临床特点及转归。方法回顾分析山东大学齐鲁医院(青岛)分别于2020年9月和12月收治的2例确诊为VGKCc抗体相关临床综合征合并伴胸腺瘤的MG患者, 总结其临床及辅助检查、随访预后等资料, 并结合相关文献进行复习总结。结果例1为64岁女性, 临床表现为认知障碍、精神异常和癫痫样发作, 血清富亮氨酸胶质瘤失活蛋白1(LGI1)抗体阳性, 明确诊断为抗LGI1脑炎, 既往存在球部起病的MG, 胸部CT提示胸腺瘤, 入院后给予免疫治疗后症状改善。例2为67岁男性, MG诊断明确, 后期出现认知功能下降、肌颤搐、自主神经症状, 神经电生理可见F波后放电及肌颤搐电位, 血清接触蛋白相关蛋白2抗体阳性, 明确诊断为莫旺综合征合并伴胸腺瘤的MG, 入院后给予免疫治疗及胸腺瘤切除等治疗, 症状改善。结论 VGKCc抗体相关临床综合征合并胸腺瘤的MG患者同时存在两类疾病各自的临床特点, 同时又有交叉。免疫治疗及针对胸腺瘤的治疗通常能取得较好的疗效。     

骨骼肌钠通道病

钠通道在神经元、骨骼肌细胞及其它大多数可兴奋细胞动作电位的起始阶段起重要作用。研究发现有10 余种与钠通道相关的遗传性疾病,其中骨骼肌钠通道病包括高钾型周期性麻痹、正常血钾型周期性麻痹、部分低钾 型周期性麻痹、先天性副肌强直、各型钾加重的肌强直等。     

电压门控钠离子通道与药物抗性癫痫

癫痫患者中约三分之一无法以现有抗癫痫药物(anti-epilep-tic drugs,AEDs)有效控制发作,称为药物抗性癫痫(drug-resist-ance epilepsy,DRE).药物抗性癫痫的主要形成机制之一是AEDs的作用靶点发生结构或功能改变,AEDs无法结合预定靶点抑制神经元过度放电,无法控制癫痫发作.电压门控性钠离子通道(voltage-gated sodium channel,VGSC)主要在可兴奋性细胞中表达,其结构和功能异常可引起神经元的膜兴奋性改变,参与癫痫的发病机制.     

电压门控钠通道、钙通道与抗Xian治疗

电压门控钠通道介导再生内向电流,这些电流负责脑神经元动作电位的初始去极化.抗痫药以及许多抑制和癫痫发作有关的异常神经元兴奋的有前景的化合物,大多是通过钠通道完成电压和频率依赖的离子电流的抑制.电压激活钙通道在控制神经元兴奋性、神经保护作用、癫癎波的发放和癎性发作的维持及传播中起重要作用.     

电压门控性钠通道β亚基与特发性癫痫

特发性癫痫与电压门控性钠通道的功能改变密切相关,β亚基作为电压门控性钠通道重要的功能调节亚基已经开始受到许多研究学者的重视。本文概述了电压门控性钠通道β亚基的基因克隆与定位、亚基分型、分子结构以及与特发性癫痫相关的功能研究现状,并介绍了由于β亚基改变而引发的特发性癫痫的相关症状。     

电压门控钠通道、钙通道与抗癎治疗

电压门控钠通道介导再生内向电流,这些电流负责脑神经元动作电位的初始去极化.抗痫药以及许多抑制和癫痫发作有关的异常神经元兴奋的有前景的化合物,大多是通过钠通道完成电压和频率依赖的离子电流的抑制.电压激活钙通道在控制神经元兴奋性、神经保护作用、癫癎波的发放和癎性发作的维持及传播中起重要作用.     

FDG-PET and MRI in potassium channel antibody-associated non-paraneoplastic limbic encephalitis: correlation with clinical course and neuropsychology

OBJECTIVES: We report a patient with potassium channel antibody-associated non-paraneoplastic limbic encephalitis (NPLE) in whom repeated fluorodeoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) are correlated with epileptic activity and memory performance during the course of disease. CASE SUMMARY: A 32-year-old woman suffered from prolonged global amnesia after two generalized tonic-clonic seizures due to NPLE. Initially, MRI showed swelling of the left hippocampus. In FDG-PET, however, bitemporomesial hypermetabolism was seen corresponding to frequent bitemporal independent seizure patterns. Also neuropsychological impairments pointed to a bitemporal involvement at this early stage. In parallel with improved control of electrographic seizure patterns, improvement was seen in FDG-PET and in memory performance. During the whole course, MRI showed only left-sided abnormalities, which correlated with a permanent verbal memory impairment. CONCLUSION: FDG-PET was more sensitive in showing the initial bitemporal involvement and correlated well with EEG findings and neuropsychological impairment in the acute phase of disease. In contrast, structural MRI better reflected persistent neuropsychological deficits.     

Voltage-gated potassium channel antibodies associated limbic encephalitis in a patient with invasive thymoma

Recently, limbic encephalitis (LE) associated with Voltage-gated potassium channel antibody (VGKC-Ab) has been postulated as a new autoimmune disorder. Most previously reported cases of VGKC-Ab-associated LE were non-paraneoplastic, and reports of a paraneoplastic type are rare. Here we describe a 59-year-old woman with paraneoplastic VGKC-Ab-associated LE preceding the recurrence of invasive thymoma. There was a close temporal relationship between the clinical course and the changes of the VGKC-Ab titer. Unlike many of the non-paraneoplastic VGKC-Ab-associated LE cases, our cases showed the more extensive high intensity lesions on MRI and the absence of seizure and hyponatremia.     

IgM-containing fraction suppressed voltage-gated potassium channels in acquired neuromyotonia

OBJECTIVES: Acquired neuromyotonia (ANM) is an autoimmune disorder caused by antibodies to voltage-gated potassium channels (VGKC). Previously, we reported a patient with immunoglobulin M (IgM), instead of immunoglobulin G (IgG), anti-VGKC antibody. The purpose of this study was to determine the function of IgM-containing fraction in ANM patients. MATERIALS AND METHODS: We determined whether anti-VGKC antibodies in the IgG or IgM-containing fractions suppressed outward potassium current (OKC) using the patch clamp method in three patients with ANM. Whole sera from all patients suppressed OKCs. RESULT: Only the purified IgG, not the IgM-containing fractions from two patients suppressed VGKCs, whereas in a patient with IgM anti-VGKC antibody, only the IgM-containing fractions, not the IgG-containing fractions suppressed VGKCs. CONCLUSION: Anti-VGKC antibodies belonging to the IgM subclass should be determined in seronegative ANM patients.     

Potassium channel antibody-associated encephalitis with hypothalamic lesions and intestinal pseudo-obstruction

A subgroup of limbic encephalitis is associated with antibodies against voltage-gated potassium channels (VGKC), and responds well to immuno-modulating therapies. Anti-VGKC antibodies are also found in Isaacs' syndrome and Morvan's syndrome, both of which are sometimes complicated by thymoma. We describe a 52-years-old man with limbic encephalitis, thymoma, and anti-VGKC antibodies, who presented with autonomic dysfunctions such as severe intestinal pseudo-obstruction, hyperhidrosis and hypertension. Thymectomy and corticosteroid therapy remarkably improved his symptoms. Brain magnetic resonance imaging showed hypothalamic lesions, in addition to the bilateral involvement of the medial temporal lobes. This patient had severe autonomic dysfunctions resembling those of Morvan's syndrome. This case may represent a subgroup of VGKC-antibody associated syndromes with a wide spectrum of symptoms, including Isaacs' syndrome, Morvan's syndrome, and limbic encephalitis.     

Potassium Channel Opener Reduces Extracellular Glutamate Concentration in Rat Focal Cerebral Ischemia

The vasodilatory action of potassium channel openers through a membrane hyperpolarizing action is well known, but little is known about the effect of these drugs on ischemia-induced glutamate release in the brain. We evaluated the effects of a potassium channel opener (Y-26763), given intravenously at 0.03 mg/kg/h from 50 min prior to occlusion until 3 h postocclusion, on cerebral blood flow, extracellular glutamate concentration, and infarct volume in rats with focal ischemia. Y-26763 significantly inhibited the increase in extracellular glutamate concentration at 50 and 60 min of ischemia with a significant reduction of mean arterial blood pressure. However, there was no significant difference in blood flow in the core of infarcted cortex or in infarct volume between Y-26763- and vehicle-treated groups. These results suggest that Y-26763 inhibited presynaptic glutamate release through hyperpolarizing the membrane, but infarct volume was not reduced because of insufficient perfusion owing to its hypotensive effect.