TRP离子通道

钙离子作为一种第二信使，在许多细胞功能中发挥着重要作用。短期的，如递质、腺体分泌，肌肉收缩；长期的，如细胞分化、程序死亡等。正常细胞都有一套完善的体系来维持钙的内稳定平衡。内质网／肌浆网的钙释放和来自质膜上钙通道的钙流入升高胞浆钙，而同时位于这两个部位的Ca^2 —泵也不断地将胞浆钙储存回钙库或泵出胞外。质膜上     

姜黄素对TRP离子通道抑制作用的研究

目的验证瞬时受体电位（TRP）通道在胶质瘤MGR2细胞中的存在,研究姜黄素对TRP通道的电生理影响,探讨姜黄素抑制肿瘤细胞增殖的可能机制。方法体外培养人脑胶质瘤细胞MGR2;利用膜片钳技术检测胶质瘤细胞MGR2的电生理特性,验证并分离TRP离子通道。使用薄荷醇、无Mg2＋内液、酸以及非特异阻断剂2-氨基乙氧基苯硼酸（2-APB）及钆离子（Gd3＋）对TRP通道的敏感性进行检测。记录不同浓度的姜黄素对TRP通道电流幅度的影响。结果神经胶质瘤细胞MGR2是一种非可兴奋细胞,其细胞上表现出TRP离子通道的电生理特性。该通道对薄荷醇不敏感,对酸的反应不明显。对细胞内液低Mg2＋有（24.2±4.1）%的TRP电流增加（n=12,P〈0.05）,200μmol/L2-APB及10μmol/LGd3＋对TRP电流分别有（46.4±4.5）%及（73.2±3.6）%的增加（n=12,P〈0.05）。姜黄素对TRP通道的抑制作用具有浓度依赖性和可恢复性。结论 TRP通道在胶质瘤细胞MGR2中存在,姜黄素对TRP通道的作用具有浓度依赖性,为姜黄素抑制肿瘤增殖的可能机制提供了实验依据。     

机械感觉相关的TRP通道研究进展

瞬时受体电位通道(transient receptor potential channels,TRP channels)是一类六次跨膜的非选择性阳离子通道,与经典离子通道主要受膜电位或配体的激活不同,TRP通道可受渗透压、pH值、机械力、配体以及细胞内信号分子等多种因素的激活,进而参与体内多种生理和病理过程,如感受痛、热等伤害刺激以及参与炎症等病理过程。近来较多的证据提示TRP通道在机械感觉中尤其有重要作用。本文对机械感觉功能相关的TRP通道,尤其是与听觉相关的TRP通道的研究进展进行综述,分析可能的激活和调控机制并展望其未来的发展方向。     

温度敏感TRP通道:从2021年诺贝尔生理学或医学奖的温度感知机制的发现到心血管和代谢的调控

2021年诺贝尔生理学或医学奖授予辣椒素受体TRPV1和薄荷醇感受器TRPM8通道的突破性发现,丰富了人们对热和冷触发的神经感知,及其适应环境温度机制的认识。温度敏感TRP通道——“热通道”TRPV1和“冷通道”TRPM8 不仅在神经系统有丰富表达,也存在于心血管、脂肪、肝脏和肌肉等组织器官,但其生物学意义并不清楚。为此,国内外学者探索温度敏感TRP通道调控心血管功能及糖脂代谢的作用,及其激动剂辣椒素和薄荷醇对心血管及代谢病的治疗效益。 2021年的诺贝尔奖使这个相对冷门的领域引起了较高的关注,并将推动其他多个领域的发展。     

肾脏病理学回顾与展望

肾脏病理学回顾与展望魏民，张月娥，张泰和病理学杂志创刊４０年来，随着现代医学的飞跃发展，肾脏病理已由既往的一般性经典性内容向目前的高水平发展。总结起来，肾脏病理主要在以下４方面的进展较为突出。一、免疫学及免疫病理学理论在肾小球疾病研究中的应用肾脏疾病...     

肝细胞生长因子与肾脏疾病

肝细胞生长因子 (HGF)是一种结构上与血液凝固级连反应的酶同源的多肽 ,其前体为无生物活性的单链 ,被丝氨酸蛋白酶裂解后成为活化的αβ异二聚体。HGF受体是MET原癌基因编码的一种跨膜酪氨酸激酶。现已证实HGF参与机体的发育过程 ,若其本身或受体的基因被敲除 ,小鼠均表现为胚胎致死的表型。此外 ,HGF还具有调节不同类型的细胞增生、有丝分裂及形态发生过程 ,因而与体内外数种肿瘤细胞的侵袭行为有关。HGF是肾脏的重要保护因子 ,通过促进肾小管上皮细胞的增生和修复能防治中毒、缺血等导致的急性肾衰 ;通过保护肾小球血管内皮细胞 ,减少肾脏的炎症反应及ECM沉积 ;通过增加胶原酶合成及抑制金属蛋白酶抑制因子生成可延缓肾纤维化的发生和发展 ;通过调节系膜细胞 上皮细胞、系膜细胞 内皮细胞之间的相互作用 ,维持肾脏的正常结构和功能     

肾脏SK通道的生理调节及分子结构

肾脏分泌性钾通道(secretory K charmel,SK channel)对于肾脏K+分泌有重要作用.分子生物学、微穿刺和微灌注等技术的联合应用使人们对SK通道的生理功能及分子结构有了较深入的认识,并已克隆出ROMK通道.本文就肾脏SK通道的生理特性、高K+摄入或醛固酮等因素对其的影响及其通道的基本分子结构进行简要综述.     

溶血磷脂酸与肾脏疾病

溶血磷脂酸是新发现具有多种生物活性的生长因子 ,通过不同的G蛋白受体介导多条信号通路 ,可引起肾系膜细胞 ,小管上皮细胞增殖 ,抑制细胞凋亡 ,参与肾脏疾病的发生发展。     

Tenascin与肾脏疾病

Tenascin(TN)是重要的细胞外基质(ECM)成分之一。在胚胎上皮器官的发生发育、肿瘤发生以及伤口愈合中发挥着非常重要的作用。本文就TN命名、分类、分子结构、功能以及其在肾脏发生发育和肾脏疾病时的表达和分布进行综述。     

细胞离子通道与疾病（3）

细胞信号转导是多种学科的交叉学科，其中离子通道（Ion Channels）的研究是交叉学科的典型，它涉及细胞生物学，物理生物学、化学生物学和免疫学等学科．离子通道信号转导通路异常引起的离子通道病就是细胞离子通道基因突变引起通道结构和功能异常与许多疾病的发生发展有关．离子通道病是指结构和／或功能异常引起的一类疾病。     

Function and regulation of TRP family channels in C. elegans

Seventeen transient receptor potential (TRP) family proteins are encoded by the C. elegans genome, and they cover all of the seven TRP subfamilies, including TRPC, TRPV, TRPM, TRPN, TRPA, TRPP, and TRPML. Classical forward and reverse genetic screens have isolated mutant alleles in every C. elegans trp gene, and their characterizations have revealed novel functions and regulatory mechanisms of TRP channels. For example, the TRPC channels TRP-1 and TRP-2 control nicotine-dependent behavior, while TRP-3, a sperm TRPC channel, is regulated by sperm activation and required for sperm–egg interactions during fertilization. Similar to their vertebrate counterparts, C. elegans TRPs function in sensory physiology. For instance, the TRPV channels OSM-9 and OCR-2 act in chemosensation, osmosensation, and touch sensation, the TRPA member TRPA-1 regulates touch sensation, while the TRPN channel TRP-4 mediates proprioception. Some C. elegans TRPM, TRPP, and TRPML members exhibit cellular functions similar to their vertebrate homologues and have provided insights into human diseases, including polycystic kidney disease, hypomagnesemia, and mucolipidosis type IV. The availability of a complete set of trp gene mutants in conjunction with its facile genetics makes C. elegans a powerful model for studying the function and regulation of TRP family channels in vivo.     

The History of the Drosophila TRP Channel: The Birth of a New Channel Superfamily

Abstract: Transient receptor potential (TRP) channels are polymodal cellular sensors involved in a wide variety of cellular processes, mainly by changing membrane voltage and increasing cellular Ca²⁺. This review outlines in detail the history of the founding member of the TRP family, the Drosophila TRP channel. The field began with a spontaneous mutation in the trp gene that led to a blind mutant during prolonged intense light. It was this mutant that allowed for the discovery of the first TRP channels. A combination of electrophysiological, biochemical, Ca²⁺ measurements, and genetic studies in flies and in other invertebrates pointed to TRP as a novel phosphoinositide-regulated and Ca²⁺-permeable channel. The cloning and sequencing of the trp gene provided its molecular identity. These seminal findings led to the isolation of the first mammalian homologues of the Drosophila TRP channels. We now know that TRP channel proteins are conserved through evolution and are found in most organisms, tissues, and cell-types. The TRP channel superfamily is classified into seven related subfamilies: TRPC, TRPM, TRPV, TRPA, TRPP, TRPML, and TRPN. A great deal is known today about participation of TRP channels in many biological processes, including initiation of pain, thermoregulation, salivary fluid secretion, inflammation, cardiovascular regulation, smooth muscle tone, pressure regulation, Ca²⁺ and Mg²⁺ homeostasis, and lysosomal function. The native Drosophila photoreceptor cells, where the founding member of the TRP channels superfamily was found, is still a useful preparation to study basic features of this remarkable channel.     

From cardiac cation channels to the molecular dissection of the transient receptor potential channel TRPM4

In 2006, we celebrate not only the milestone paper on the patch-clamp technique [14] but also the publication of the first single-channel measurements in cardiac cells revealing a Ca²⁺-activated, nonselective cation channel [6]. Considerable effort has been undertaken since this time to identify molecular candidates for this class of cation channels that can be found in a variety of tissues. Recent work has shown that this channel is very likely TRPM4, a member of the TRPM ion channel family. The current review links the epochal Colquhoun et al. paper to the detailed molecular knowledge and structure function aspects of this TRP channel. It will be shown that TRPM4 is a Ca²⁺- and voltage-activated channel, which is dramatically modulated by the phospholipid phosphatidyl inositol bisphosphate (PIP₂) and belongs to the heat-activated thermoTRPs. A functional hallmark of TRPM4, as for several TRP channels, is a dramatic shift of its voltage dependence towards negative, physiologically meaningful potentials.     

Regulation of TRP channels by PIP2

Transient receptor potential (TRP) channels are regulated by a wide variety of physical and chemical factors. Recently, several members of the TRP channel family were reported to be regulated by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂, PIP₂). This review will summarize the current knowledge on PIP₂ regulation of TRP channels and discuss the possibility that PIP₂ is a common regulator of mammalian TRP channels.     

Invertebrate TRP proteins as functional models for mammalian channels

Transient receptor potential (TRP) channels constitute a large and diverse family of channel proteins that are expressed in many tissues and cell types in both vertebrates and invertebrates. While the biophysical features of many of the mammalian TRP channels have been described, relatively little is known about their biological roles. Invertebrate TRPs offer valuable genetic handles for characterizing the functions of these cation channels in vivo. Importantly, studies in model organisms can help to identify fundamental mechanisms involved in normal cellular functions and human disease. In this review, we give an overview of the different TRP channels known in the two most utilized invertebrate models, the nematode Caenorhabditis elegans and the fruit-fly Drosophila melanogaster, and discuss briefly the heuristic impact of these invertebrate channels with respect to TRP function in mammals.     

Drosophila TRP channels

The transient receptor potential (TRP) superfamily comprises a large group of related cation channels that display surprising diversity in the specific modes of activation and cation selectivities. However, a unifying theme is that many TRP channels play important roles in sensory physiology. The superfamily includes 28 mammalian members, which are subdivided into multiple subfamilies. Each of these subfamilies is represented by at least one of the 13 members in Drosophila, suggesting common evolutionary relationships. In recent years it has become clear that TRP channels in flies and mammals participate in similar sensory modalities. These include, but are not limited to, hearing, thermosensation, and certain specialized types of vision. With the recent flurry of new studies, 9 out of the 13 TRPs have been addressed in various contexts. As a result, the repertoire of biological roles attributed to Drosophila TRPs has increased considerably and is likely to lead to many additional surprises over the next few years.     

S100A10/p11: family, friends and functions

S100A10, also known as p11 or annexin 2 light chain, is a member of the S100 family of small, dimeric EF hand-type Ca²⁺-binding proteins that generally modulate cellular target proteins in response to intracellular Ca²⁺ signals. In contrast to all other S100 proteins, S100A10 is Ca²⁺ insensitive because of amino acid replacements in its Ca²⁺-binding loops that lock the protein in a permanently active state. Within cells, the majority of S100A10 resides in a tight heterotetrameric complex with the peripheral membrane-binding protein annexin A2 that directs the complex to specific target membranes, in particular the plasma membrane and the membrane of early endosomes. Several other Ca²⁺-independent interaction partners of S100A10 have been described in the recent past. Many of these interactions, which have been shown to be of functional significance for the respective partner, involve plasma membrane-resident proteins. In most of these cases, S100A10, probably residing in a complex with annexin A2, appears to regulate the intracellular trafficking of the respective target protein and thus its functional expression at the cell surface. In this paper, we review the current information on S100A10 protein interactions placing a particular emphasis on data that contribute to an understanding of the mechanistic basis of the S100A10 action. Based on these data, we propose that S100A10 functions as a linker tethering certain transmembrane proteins to annexin A2 thereby assisting their traffic to the plasma membrane and/or their firm anchorage at certain membrane sites.     

Isolation of the TRP2 and the TRP3 genes of Saccharomyces cerevisiae by functional complementation in yeast

Summary This paper describes the isolation of the TRP2 and the TRP3 genes of Saccharomyces cerevisiae. Two pools of plasmids consisting of BamHI and Sa1GI yeast DNA inserts into the bifunctional yeast — Escherichia coli vector pLC544 (Kingsman et al. 1979) were constructed in E. coli and used for the isolation of the two genes by selection for functional complementation of trp2 and trp3 mutations, respectively, in yeast.The TRP2 gene was isolated on a 6.2 kb BamHl and a 5.8 kb Sa1GI yeast DNA fragment which shared an identical 4.5 kb BamHI-SaIGI fragment. The TRP3 gene was located on a 5.2 kb BamHl fragment.By physical, genetic and physiological experiments it could be shown that the cloned yeast DNA fragments contained the whole structural sequences as well as the regulatory regions of the TRP2 and the TRP3 genes.     

TRAM-34 inhibits nonselective cation channels

TRAM-34 has been demonstrated to inhibit intermediate-conductance Ca²⁺-activated K⁺ channels in a wide variety of cell types, including immune cells. In the present study, we investigated effects of TRAM-34 on microglial cells stimulated with lysophosphatidylcholine (LPC). LPC-induced increases in the intracellular Ca²⁺ concentration of microglial cells were effectively reduced in the presence of TRAM-34. At a concentration of 1 μM, TRAM-34 inhibited LPC-induced Ca²⁺ signals by 60%. The TRAM-34-induced reduction of LPC-induced Ca²⁺ increases cannot be related to the inhibition of Ca²⁺-activated K⁺ channels. In contrast to TRAM-34, the Ca²⁺-activated K⁺ channel inhibitor charybdotoxin did not affect LPC-induced increases in the intracellular Ca²⁺ concentration of microglial cells. Patch clamp experiments revealed a direct inhibitory effect of TRAM-34 on nonselective cation channels. Half-maximal inhibition of LPC-induced nonselective cation currents was determined at 38 nM TRAM-34. These data indicate that TRAM-34 may cause additional effects on immune cells that are unrelated to the well-described inhibition of Ca²⁺-activated K⁺ channels.