Ion channelopathies in functional GI disorders
Ion channelopathies in functional GI disorders
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DOI：
10.1152/ajpgi.00237.2016
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发表时间：
2016-10-01
影响因子：
4.5
通讯作者：
Farrugia, Gianrico
中科院分区：
文献类型：
--
作者：
Beyder, Arthur;Farrugia, Gianrico
在胃肠道（GI）中，分泌、吸收、运动和感觉的异常与功能性胃肠道疾病（fgid）有关。离子通道在所有这些胃肠道功能中起着重要作用。离子通道传导离子的能力被破坏会导致被称为离子通道病的疾病。离子通道病变可能是由于突变、翻译后修饰和辅助蛋白功能障碍导致离子通道生物物理功能或表达的改变。通道病在心脏病学和神经学领域已经得到了强有力的建立，但离子通道病在胃肠病学中才刚刚开始被认识到。在这篇综述中，我们描述了GI离子通道病变的新兴领域的状态。最近的一些发现表明，通道病导致胃肠道运动、分泌和感觉的改变。在上皮中，囊性纤维化跨膜传导调节因子（CFTR）或CFTR相关蛋白的突变导致以便秘或腹泻为表型的通道病。在肌肉中，scn5a编码的电压门控钠通道NaV1.5的突变与肠易激综合征有关。在感觉神经中，电压门控钠通道NaV1.7和NaV1.9（分别由SCN9A和SCN11A编码）的通道病变表现为GI亢进或亢进。结构生物学和离子通道生物物理学的最新进展，加上个性化医疗，推动了新型通道病变的快速发现和特定通道病变的直接药物靶向。总之，胃肠道离子通道病变这一新兴领域对功能性胃肠道疾病的分层、诊断和治疗具有重要意义。
In the gastrointestinal (GI) tract, abnormalities in secretion, absorption, motility, and sensation have been implicated in functional gastrointestinal disorders (FGIDs). Ion channels play important roles in all these GI functions. Disruptions of ion channels' ability to conduct ions can lead to diseases called ion channelopathies. Channelopathies can result from changes in ion channel biophysical function or expression due to mutations, posttranslational modification, and accessory protein malfunction. Channelopathies are strongly established in the fields of cardiology and neurology, but ion channelopathies are only beginning to be recognized in gastroenterology. In this review, we describe the state of the emerging field of GI ion channelopathies. Several recent discoveries show that channelopathies result in alterations in GI motility, secretion, and sensation. In the epithelium, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) or CFTR-associating proteins result in channelopathies with constipation or diarrhea as phenotypes. In the muscle, mutations in the SCN5A-encoded voltage-gated sodium channel NaV1.5 are associated with irritable bowel syndrome. In the sensory nerves, channelopathies of voltage-gated sodium channels NaV1.7 and NaV1.9 (encoded by SCN9A, SCN11A, respectively) manifest by either GI hyper- or hyposensation. Recent advances in structural biology and ion channel biophysics, coupled with personalized medicine, have fueled rapid discoveries of novel channelopathies and direct drug targeting of specific channelopathies. In summary, the emerging field of GI ion channelopathies has significant implications for functional GI disease stratification, diagnosis, and treatment.