Human K(ATP) channelopathies: diseases of metabolic homeostasis.
Human K(ATP) channelopathies: diseases of metabolic homeostasis.
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DOI：
10.1007/s00424-009-0771-y
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发表时间：
2010-07
影响因子：
4.5
通讯作者：
Terzic, Andre
中科院分区：
文献类型：
--
作者：
Olson, Timothy M.;Terzic, Andre
关键词：
内向整流钾通道孔（Kir6.1/Kir6.2）和三磷酸腺苷（ATP）结合调节亚基（SUR 1/SUR 2A/SUR 2B）的组装形成ATP敏感性钾（KATP）通道异多聚体，广泛分布于全身代谢活性组织中。KATP通道是代谢门控的生物传感器，其功能是调节膜电位依赖性功能以匹配细胞能量需求的分子变阻器。KATP通道在对（病理）生理应激的适应性反应中至关重要，具有从葡萄糖调节到心脏保护的稳态作用。因此，KATP通道亚基的遗传变异与危及生命的人类疾病的病因学有关。特别是，已在胰岛素分泌障碍，即先天性高胰岛素血症和新生儿糖尿病中鉴定出KATP通道的致病突变。此外，KATP通道缺陷是发育迟缓、癫痫和新生儿糖尿病（DEND综合征）三联征的基础。与机械性和/或电性心脏病患者相关的KATP通道病包括扩张型心肌病（伴室性心律失常; CMD 10）和肾上腺素能性房颤。一种常见的Kir6.2 E23 K多态性与晚发性糖尿病相关，并作为社区中适应不良心脏重塑和心力衰竭患者心肺运动应激表现异常的危险因素。KATP通道基因内的总体突变频率和基因型-表型关系的谱仍有待建立，而通过系统生物学方法预测通道功能缺陷的后果正变得越来越可行。因此，在人类KATP通道病的新兴领域中，分子医学的进展为靶向个体化筛查、早期诊断和定制治疗提供了新的机会。
Assembly of an inward rectifier K+ channel pore (Kir6.1/Kir6.2) and an adenosine triphosphate (ATP)-binding regulatory subunit (SUR1/SUR2A/SUR2B) forms ATP-sensitive K+ (KATP) channel heteromultimers, widely distributed in metabolically active tissues throughout the body. KATP channels are metabolism-gated biosensors functioning as molecular rheostats that adjust membrane potential-dependent functions to match cellular energetic demands. Vital in the adaptive response to (patho)physiological stress, KATP channels serve a homeostatic role ranging from glucose regulation to cardioprotection. Accordingly, genetic variation in KATP channel subunits has been linked to the etiology of life-threatening human diseases. In particular, pathogenic mutations in KATP channels have been identified in insulin secretion disorders, namely, congenital hyperinsulinism and neonatal diabetes. Moreover, KATP channel defects underlie the triad of developmental delay, epilepsy, and neonatal diabetes (DEND syndrome). KATP channelopathies implicated in patients with mechanical and/or electrical heart disease include dilated cardiomyopathy (with ventricular arrhythmia; CMD1O) and adrenergic atrial fibrillation. A common Kir6.2 E23K polymorphism has been associated with late-onset diabetes and as a risk factor for maladaptive cardiac remodeling in the community-at-large and abnormal cardiopulmonary exercise stress performance in patients with heart failure. The overall mutation frequency within KATP channel genes and the spectrum of genotype–phenotype relationships remain to be established, while predicting consequences of a deficit in channel function is becoming increasingly feasible through systems biology approaches. Thus, advances in molecular medicine in the emerging field of human KATP channelopathies offer new opportunities for targeted individualized screening, early diagnosis, and tailored therapy.
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影响因子：
4.8
作者：
Bienengraeber, M;Alekseev, AE;Terzic, A
通讯作者：
Terzic, A
影响因子：
4.4
作者：
Arrell, D. Kent;Zlatkovic, Jelena;Kane, Garvan C.;Yamada, Satsuki;Terzic, Andre
通讯作者：
Terzic, Andre
影响因子：
4.8
作者：
Abraham, MR;Selivanov, VA;Terzic, A
通讯作者：
Terzic, A
DOI：
10.1016/s0022-2828(03)00246-3
发表时间：
2003-12-01
影响因子：
5
作者：
Balana, B;Dobrev, D;Ravens, U
通讯作者：
Ravens, U
影响因子：
7.7
作者：
Chutkow, WA;Simon, MC;Burant, CF
通讯作者：
Burant, CF