Channels (Austin, Tex.)最新文献_第5页

Plant and fungi derived analgesic natural products targeting voltage-gated sodium and calcium channels. 靶向电压门控钠钙通道的植物和真菌衍生镇痛天然产物。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2103234

Aida Calderon-Rivera, Santiago Loya-Lopez, Kimberly Gomez, Rajesh Khanna

{"title":"Plant and fungi derived analgesic natural products targeting voltage-gated sodium and calcium channels.","authors":"Aida Calderon-Rivera, Santiago Loya-Lopez, Kimberly Gomez, Rajesh Khanna","doi":"10.1080/19336950.2022.2103234","DOIUrl":"https://doi.org/10.1080/19336950.2022.2103234","url":null,"abstract":"Voltage-gated sodium and calcium channels (VGSCs and VGCCs) play an important role in the modulation of physiologically relevant processes in excitable cells that range from action potential generation to neurotransmission. Once their expression and/or function is altered in disease, specific pharmacological approaches become necessary to mitigate the negative consequences of such dysregulation. Several classes of small molecules have been developed with demonstrated effectiveness on VGSCs and VGCCs; however, off-target effects have also been described, limiting their use and spurring efforts to find more specific and safer molecules to target these channels. There are a great number of plants and herbal preparations that have been empirically used for the treatment of diseases in which VGSCs and VGCCs are involved. Some of these natural products have progressed to clinical trials, while others are under investigation for their action mechanisms on signaling pathways, including channels. In this review, we synthesize information from ~30 compounds derived from natural sources like plants and fungi and delineate their effects on VGSCs and VGCCs in human disease, particularly pain. [Figure: see text].","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"16 1","pages":"198-215"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9423853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10631869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Rab35 GTPase positively regulates endocytic recycling of cardiac K_ATP channels. Rab35 GTPase正调控心脏KATP通道的内吞循环。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2090667

Bo Yang, Jia-Lu Yao, Jian-Yi Huo, Yu-Long Feng, William A Coetzee, Guang-Yin Xu, Hua-Qian Yang

{"title":"Rab35 GTPase positively regulates endocytic recycling of cardiac KATP channels.","authors":"Bo Yang, Jia-Lu Yao, Jian-Yi Huo, Yu-Long Feng, William A Coetzee, Guang-Yin Xu, Hua-Qian Yang","doi":"10.1080/19336950.2022.2090667","DOIUrl":"https://doi.org/10.1080/19336950.2022.2090667","url":null,"abstract":"ATP-sensitive K+ (KATP) channel couples membrane excitability to intracellular energy metabolism. Maintaining KATP channel surface expression is key to normal insulin secretion, blood pressure and cardioprotection. However, the molecular mechanisms regulating KATP channel internalization and endocytic recycling, which directly affect the surface expression of KATP channels, are poorly understood. Here we used the cardiac KATP channel subtype, Kir6.2/SUR2A, and characterized Rab35 GTPase as a key regulator of KATP channel endocytic recycling. Electrophysiological recordings and surface biotinylation assays showed decreased KATP channel surface density with co-expression of a dominant negative Rab35 mutant (Rab35-DN), but not other recycling-related Rab GTPases, including Rab4, Rab11a and Rab11b. Immunofluorescence images revealed strong colocalization of Rab35-DN with recycling Kir6.2. Rab35-DN minimized the recycling rate of KATP channels. Rab35 also regulated KATP channel current amplitude in isolated adult cardiomyocytes by affecting its surface expression but not channel properties, which validated its physiologic relevance and the potential of pharmacologic target for treating the diseases with KATP channel trafficking defects.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"137-147"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40401102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring mutation specific beta blocker pharmacology of the pathogenic late sodium channel current from patient-specific pluripotent stem cell myocytes derived from long QT syndrome mutation carriers. 探索突变特异性β受体阻滞剂对来自长QT综合征突变携带者的患者特异性多能干细胞肌细胞致病性晚期钠通道电流的药理学作用。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2106025

Thomas W Comollo, Xinle Zou, Chuangeng Zhang, Divya Kesters, Thomas Hof, Kevin J Sampson, Robert S Kass

{"title":"Exploring mutation specific beta blocker pharmacology of the pathogenic late sodium channel current from patient-specific pluripotent stem cell myocytes derived from long QT syndrome mutation carriers.","authors":"Thomas W Comollo, Xinle Zou, Chuangeng Zhang, Divya Kesters, Thomas Hof, Kevin J Sampson, Robert S Kass","doi":"10.1080/19336950.2022.2106025","DOIUrl":"https://doi.org/10.1080/19336950.2022.2106025","url":null,"abstract":"The congenital long QT syndrome (LQTS), one of the most common cardiac channelopathies, is characterized by delayed ventricular repolarization underlying prolongation of the QT interval of the surface electrocardiogram. LQTS is caused by mutations in genes coding for cardiac ion channels or ion channel-associated proteins. The major therapeutic approach to LQTS management is beta blocker therapy which has been shown to be effective in treatment of LQTS variants caused by mutations in K+ channels. However, this approach has been questioned in the treatment of patients identified as LQTS variant 3(LQT3) patients who carry mutations in SCN5A, the gene coding for the principal cardiac Na+ channel. LQT3 mutations are gain of function mutations that disrupt spontaneous Na+ channel inactivation and promote persistent or late Na+ channel current (INaL) that delays repolarization and underlies QT prolongation. Clinical investigation of patients with the two most common LQT3 mutations, the ΔKPQ and the E1784K mutations, found beta blocker treatment a useful therapeutic approach for managing arrhythmias in this patient population. However, there is little experimental data that reveals the mechanisms underlying these antiarrhythmic actions. Here, we have investigated the effects of the beta blocker propranolol on INaL expressed by ΔKPQ and E1784K channels in induced pluripotent stem cells derived from patients carrying these mutations. Our results indicate that propranolol preferentially inhibits INaL expressed by these channels suggesting that the protective effects of propranolol in treating LQT3 patients is due in part to modulation of INaL.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"16 1","pages":"173-184"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9373745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10637560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Piezo1 activation facilitates ovarian cancer metastasis via Hippo/YAP signaling axis. Piezo1激活通过Hippo/YAP信号轴促进卵巢癌转移。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2099381

Yanjie Xiong, Liru Dong, Yun Bai, Hui Tang, Shuang Li, Dan Luo, Fang Liu, Jie Bai, Shikun Yang, Xudong Song

{"title":"Piezo1 activation facilitates ovarian cancer metastasis via Hippo/YAP signaling axis.","authors":"Yanjie Xiong, Liru Dong, Yun Bai, Hui Tang, Shuang Li, Dan Luo, Fang Liu, Jie Bai, Shikun Yang, Xudong Song","doi":"10.1080/19336950.2022.2099381","DOIUrl":"https://doi.org/10.1080/19336950.2022.2099381","url":null,"abstract":"Ovarian cancer (OC) is a highly malignant cancer with great metastatic potential. Here we aimed to investigate the role of Piezo1, a gene related to the mechanical environment of the tumor, in promoting the metastasis of OC. We performed Piezo1 knockdown in A-1847 cells using small hairpin RNAs, and the cells were inoculated subcutaneously in nude mice. Piezo1 knockdown decreased the tumor growth rate of OC tumor xenografts in mice and reduced cell migration in vitro. Metastasis in the lung was also attenuated after Piezo1 knockdown as revealed by HE staining of the lung tissues, which was concomitant with downregulation of E-Cadherin and vimentin and upregulation of N-Cadherin analyzed using western blot analysis, suggesting suppressed epithelial-to-mesenchymal transition. Migration of Piezo1-knockdown cells was also analyzed for their migratory capabilities using the scratch assay. We also analyzed the key proteins in the Hippo/YAP signaling pathway using western blot after treating A-1847 and 3AO cells with a Piezo1 inducer, Yoda1. Piezo1 inducer Yoda1 activated Hippo/YAP signal in OC cells. In conclusion, Piezo1 is overexpressed in OC tissues and contributes to OC tumor growth and metastasis. Suppression of Piezo1 is a potential therapeutic strategy for OC.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"159-166"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40612286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Non-conducting functions of ion channels: The case of integrin-ion channel complexes. 离子通道的非导电功能:整合离子通道复合物的情况。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2108565

Elena Forzisi, Federico Sesti

{"title":"Non-conducting functions of ion channels: The case of integrin-ion channel complexes.","authors":"Elena Forzisi, Federico Sesti","doi":"10.1080/19336950.2022.2108565","DOIUrl":"https://doi.org/10.1080/19336950.2022.2108565","url":null,"abstract":"Started as an academic curiosity more than two decades ago, the idea that ion channels can regulate cellular processes in ways that do not depend on their conducting properties (non-ionic functions) gained traction and is now a flourishing area of research. Channels can regulate physiological processes including actin cytoskeletal remodeling, cell motility, excitation-contraction coupling, non-associative learning and embryogenesis, just to mention some, through non-ionic functions. When defective, non-ionic functions can give rise to channelopathies involved in cancer, neurodegenerative disease and brain trauma. Ion channels exert their non-ionic functions through a variety of mechanisms that range from physical coupling with other proteins, to possessing enzymatic activity, to assembling with signaling molecules. In this article, we take stock of the field and review recent findings. The concept that emerges, is that one of the most common ways through which channels acquire non-ionic attributes, is by assembling with integrins. These integrin-channel complexes exhibit broad genotypic and phenotypic heterogeneity and reveal a pleiotropic nature, as they appear to be capable of influencing both physiological and pathological processes.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"185-197"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

A SWELL time to develop the molecular pharmacology of the volume-regulated anion channel (VRAC). 体积调节阴离子通道(VRAC)的分子药理学研究是一个非常好的时期。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2033511

Eric E Figueroa, Jerod S Denton

引用次数: 6

Pleiotropic Ankyrins: Scaffolds for Ion Channels and Transporters. 多效性锚定蛋白:离子通道和转运体的支架。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2120467

Sharon R Stevens, Matthew N Rasband

引用次数: 3

Clinical and molecular characteristics of myotonia congenita in China: Case series and a literature review. 中国先天性肌强直的临床和分子特征:病例系列和文献回顾。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2041292

Yifan Li, Mao Li, Zhenfu Wang, Fei Yang, Hongfen Wang, Xiujuan Bai, Bo Sun, Siyu Chen, Xusheng Huang

{"title":"Clinical and molecular characteristics of myotonia congenita in China: Case series and a literature review.","authors":"Yifan Li, Mao Li, Zhenfu Wang, Fei Yang, Hongfen Wang, Xiujuan Bai, Bo Sun, Siyu Chen, Xusheng Huang","doi":"10.1080/19336950.2022.2041292","DOIUrl":"https://doi.org/10.1080/19336950.2022.2041292","url":null,"abstract":"Myotonia congenita (MC) is a rare genetic disease caused by mutations in the skeletal muscle chloride channel gene (CLCN1), encoding the voltage-gated chloride channel ClC-1 in skeletal muscle. Our study reported the clinical and molecular characteristics of six patients with MC and systematically review the literature on Chinese people. We retrospectively analyzed demographics, clinical features, family history, creatine kinase (CK), electromyography (EMG), treatment, and genotype data of our patients and reviewed the clinical data and CLCN1 mutations in literature. The median ages at examination and onset were 26.5 years (range 11-50 years) and 6.5 years (range 1.5-11 years), respectively, in our patients, and 21 years (range 3.5-65 years, n = 45) and 9 years (range 0.5-26 years, n = 50), respectively, in literature. Similar to previous reports, myotonia involved limb, lids, masticatory, and trunk muscles to varying degrees. Warm-up phenomenon (5/6), percussion myotonia (3/5), and grip myotonia (6/6) were common. Menstruation triggered myotonia in females, not observed in Chinese patients before. The proportion of abnormal CK levels (4/5) was higher than data from literature. Electromyography performed in six patients revealed myotonic changes (100%). Five novel CLCN1 mutations, including a splicing mutation (c.853 + 4A>G), a deletion mutation (c.2010_2014del), and three missense mutations (c.2527C>T, c.1727C>T, c.2017 G > C), were identified. The c.892 G > A (p.A298T) mutation was the most frequent mutation in the Chinese population. Our study expanded the clinical and genetic spectrum of patients with MC in the China. The MC phenotype in Chinese people is not different from that found in the West, while the genotype is different.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"35-46"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

AMP-activated protein kinase(AMPK) channel: A Global Bibliometric analysis From 2012 to 2021. amp活化蛋白激酶(AMPK)通道:2012 - 2021年全球文献计量分析

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2049543

Tianyi Lyu, Chuanxi Tian, Tianyang Tan, Jiaxuan Lyu, Kang Yan, Xirui Zhao, Ruoshui Wang, Chaoyang Zhang, Meng Liu, Yulong Wei

引用次数: 5

Genetic and cellular characterization of MscS-like putative channels in the filamentous fungus Aspergillus nidulans. 丝状真菌细粒曲霉(Aspergillus nidulans)中msc样通道的遗传和细胞特性。

Channels (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19336950.2022.2098661

Mariangela Dionysopoulou, Nana Yan, Bolin Wang, Christos Pliotas, George Diallinas

{"title":"Genetic and cellular characterization of MscS-like putative channels in the filamentous fungus Aspergillus nidulans.","authors":"Mariangela Dionysopoulou, Nana Yan, Bolin Wang, Christos Pliotas, George Diallinas","doi":"10.1080/19336950.2022.2098661","DOIUrl":"https://doi.org/10.1080/19336950.2022.2098661","url":null,"abstract":"Mechanosensitive ion channels are integral membrane proteins ubiquitously present in bacteria, archaea, and eukarya. They act as molecular sensors of mechanical stress to serve vital functions such as touch, hearing, osmotic pressure, proprioception and balance, while their malfunction is often associated with pathologies. Amongst them, the structurally distinct MscL and MscS channels from bacteria are the most extensively studied. MscS-like channels have been found in plants and Schizosaccharomyces pombe, where they regulate intracellular Ca2+ and cell volume under hypo-osmotic conditions. Here we characterize two MscS-like putative channels, named MscA and MscB, from the model filamentous fungus Aspergillus nidulans. Orthologues of MscA and MscB are present in most fungi, including relative plant and animal pathogens. MscA/MscB and other fungal MscS-like proteins share the three transmembrane helices and the extended C-terminal cytosolic domain that form the structural fingerprint of MscS-like channels with at least three additional transmembrane segments than Escherichia coli MscS. We show that MscA and MscB localize in Endoplasmic Reticulum and the Plasma Membrane, respectively, whereas their overexpression leads to increased CaCl2 toxicity or/and reduction of asexual spore formation. Our findings contribute to understanding the role of MscS-like channels in filamentous fungi and relative pathogens.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"148-158"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40611172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3