Pore directions for the expression of a Ca2+-activated chloride channel.
Pore directions for the expression of a Ca2+-activated chloride channel.
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Ca2 激活氯离子通道表达的孔方向。
DOI：
10.1113/jphysiol.2013.258160
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Schultz,BruceD
中科院分区：
文献类型：
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作者：
Schultz,BruceD
在确定胞质Ca 2+如何可能有助于调节膜电位、细胞兴奋性、离子转运和感觉方面已经迈出了重要一步。在这一期的生理学杂志上，Adomaviciene et al.（2013）暗示Ca 2+激活的氯离子通道（CaCC）中推定孔的一部分作为非典型Ca 2+敏感区域，其增强通道在细胞膜中的驻留。关于表达CaCCs的细胞中Ca 2+浓度和膜电位之间的时间依赖性相互作用仍存在许多问题。虽然这些意见提出了一个假定的细胞外环的定位和阴离子渗透途径的结构的问题，他们提供了一个新的方向，在该领域的表征CaCCs.Much的努力已经花费了超过三十年来定义的分子基础的CaCCs。第一个目标是定义分子身份和结构，其解释了归因于CaCC的生理功能，包括上皮离子转运、平滑肌收缩、嗅觉、味觉、光感受、躯体感觉和受精。一旦确定，CaCC将成为治疗或规避各种疾病的潜在药物靶点，包括癌症和囊性纤维化。也许无意中，2003年，随着染色体11基因的鉴定，定义CaCC迈出了重要一步，该基因编码在食道、膀胱和乳腺肿瘤中表达的推定跨膜蛋白，最终被命名为Tmem 16 a（Katoh，2003）。该原始鉴定包括观察到表达了两种剪接变体（含/不含外显子15）。计算机模拟分析显示，Tmem 16 a是
A major step has been made in determining how cytosolic Ca2+ might contribute to the regulation of membrane potential, cell excitability, ion transport and sensation. In this issue of The Journal of Physiology, Adomaviciene et al.(2013) implicate a portion of a putative pore in Ca2+-activated chloride channels (CaCCs) as a non-canonical Ca2+-sensitive region that enhances channel residency in the cell membrane. Many questions remain regarding the time-dependent interplay between Ca2+ concentration and membrane potential in cells expressing CaCCs. While these observations raise questions regarding the positioning of a putative extracellular loop and the structure of the anion permeation pathway, they provide a new direction for the field in the characterization of CaCCs.Much effort has been expended over more than three decades to define the molecular basis of CaCCs. A first goal is to define the molecular identity and structure that accounts for the physiological functions that have been attributed to CaCCs, including epithelial ion transport, smooth muscle contraction, olfaction, gustation, photoreception, somatic sensation and fertilization. Once defined, CaCCs would constitute potential drugable targets to treat or circumvent a variety of diseases, including cancer and cystic fibrosis. Perhaps unwittingly, a major step in defining CaCCs was made in 2003 with the identification of a chromosome11 gene that coded for a putative transmembrane protein that was expressed in oesophageal, bladder and breast tumours, which was ultimately named Tmem16a (Katoh, 2003). This original identification included the observation that two splice variants (with/without exon 15) were expressed. In silico analysis revealed that Tmem16a was