Channels (Austin, Tex.)最新文献_第3页

Clinical and genetic characteristics of myotonia congenita in Chinese population. 中国人群先天性肌张力障碍的临床和遗传特征

Channels (Austin, Tex.) Pub Date : 2024-12-01 Epub Date: 2024-05-08 DOI: 10.1080/19336950.2024.2349823

Yuting He, Yusen Qiu, Ying Xiong, Yu Shen, Kaiyan Jiang, Hancun Yi, Pengcheng Huang, Yu Zhu, Min Zhu, Meihong Zhou, Daojun Hong, Dandan Tan

{"title":"Clinical and genetic characteristics of myotonia congenita in Chinese population.","authors":"Yuting He, Yusen Qiu, Ying Xiong, Yu Shen, Kaiyan Jiang, Hancun Yi, Pengcheng Huang, Yu Zhu, Min Zhu, Meihong Zhou, Daojun Hong, Dandan Tan","doi":"10.1080/19336950.2024.2349823","DOIUrl":"10.1080/19336950.2024.2349823","url":null,"abstract":"Myotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"18 1","pages":"2349823"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892497","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

Ionotropic purinergic receptor 7 (P2X7) channel structure and pharmacology provides insight regarding non-nucleotide agonism. 离子型嘌呤能受体 7（P2X7）通道结构和药理学提供了有关非核苷酸激动作用的见解。

Channels (Austin, Tex.) Pub Date : 2024-12-01 Epub Date: 2024-05-19 DOI: 10.1080/19336950.2024.2355150

Rua'a Al-Aqtash, Daniel M Collier

{"title":"Ionotropic purinergic receptor 7 (P2X7) channel structure and pharmacology provides insight regarding non-nucleotide agonism.","authors":"Rua'a Al-Aqtash, Daniel M Collier","doi":"10.1080/19336950.2024.2355150","DOIUrl":"10.1080/19336950.2024.2355150","url":null,"abstract":"P2X7 is a member of the Ionotropic Purinergic Receptor (P2X) family. The P2X family of receptors is composed of seven (P2X1-7), ligand-gated, nonselective cation channels. Changes in P2X expression have been reported in multiple disease models. P2Xs have large complex extracellular domains that function as receptors for a variety of ligands, including endogenous and synthetic agonists and antagonists. ATP is the canonical agonist. ATP affinity ranges from nanomolar to micromolar for most P2XRs, but P2X7 has uniquely poor ATP affinity. In many physiological settings, it may be difficult to achieve the millimolar extracellular ATP concentrations needed for P2X7 channel activation; however, channel function is implicated in pain sensation, immune cell function, cardiovascular disease, cancer, and osteoporosis. Multiple high-resolution P2X7 structures have been solved in apo-, ATP-, and antagonist-bound states. P2X7 structural data reveal distinct allosteric and orthosteric antagonist-binding sites. Both allosteric and orthosteric P2X7 antagonists are well documented to inhibit ATP-evoked channel current. However, a growing body of evidence supports P2X7 activation by non-nucleotide agonists, including extracellular histone proteins and human cathelicidin-derived peptides (LL-37). Interestingly, P2X7 non-nucleotide agonism is not inhibited by allosteric antagonists, but is inhibited by orthosteric antagonists. Herein, we review P2X7 function with a focus on the efficacy of available pharmacology on P2X7 channel current activation by non-nucleotide agonists in effort to understand agonist/antagonist efficacy, and consider the impact of these data on the current understanding of P2X7 in physiology and disease given these limitations of P2X7-selective antagonists and incomplete knockout mouse models.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"18 1","pages":"2355150"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066102","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

Recent advances on the structure and the function relationships of the TRPV4 ion channel. TRPV4 离子通道结构与功能关系的最新进展。

Channels (Austin, Tex.) Pub Date : 2024-12-01 Epub Date: 2024-02-14 DOI: 10.1080/19336950.2024.2313323

Raúl Sánchez-Hernández, Miguel Benítez-Angeles, Ana M Hernández-Vega, Tamara Rosenbaum

{"title":"Recent advances on the structure and the function relationships of the TRPV4 ion channel.","authors":"Raúl Sánchez-Hernández, Miguel Benítez-Angeles, Ana M Hernández-Vega, Tamara Rosenbaum","doi":"10.1080/19336950.2024.2313323","DOIUrl":"10.1080/19336950.2024.2313323","url":null,"abstract":"The members of the superfamily of Transient Receptor Potential (TRP) ion channels are physiologically important molecules that have been studied for many years and are still being intensively researched. Among the vanilloid TRP subfamily, the TRPV4 ion channel is an interesting protein due to its involvement in several essential physiological processes and in the development of various diseases. As in other proteins, changes in its function that lead to the development of pathological states, have been closely associated with modification of its regulation by different molecules, but also by the appearance of mutations which affect the structure and gating of the channel. In the last few years, some structures for the TRPV4 channel have been solved. Due to the importance of this protein in physiology, here we discuss the recent progress in determining the structure of the TRPV4 channel, which has been achieved in three species of animals (Xenopus tropicalis, Mus musculus, and Homo sapiens), highlighting conserved features as well as key differences among them and emphasizing the binding sites for some ligands that play crucial roles in its regulation.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"18 1","pages":"2313323"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736869","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

Characterization of four structurally diverse inhibitors of SUR2-containing K_ATP channels. 含 SUR2 的 KATP 通道的四种结构不同的抑制剂的特性。

Channels (Austin, Tex.) Pub Date : 2024-12-01 Epub Date: 2024-09-20 DOI: 10.1080/19336950.2024.2398565

Kangjun Li, Vaishali Satpute Janve, Jerod Denton

{"title":"Characterization of four structurally diverse inhibitors of SUR2-containing KATP channels.","authors":"Kangjun Li, Vaishali Satpute Janve, Jerod Denton","doi":"10.1080/19336950.2024.2398565","DOIUrl":"10.1080/19336950.2024.2398565","url":null,"abstract":"Vascular smooth muscle ATP-sensitive potassium (KATP) channels play critical roles in modulating vascular tone and thus represent important drug targets for diverse cardiovascular pathologies. Despite extensive research efforts spanning several decades, the search for selective inhibitors that can discriminate between vascular KATP (i.e. Kir6.1/SUR2B) and pancreatic and brain KATP (i.e. Kir6.2/SUR1) channels has, until recently, been unsuccessful. Our group therefore carried out a high-throughput screen of chemically diverse compounds with the goal of discovering specific Kir6.1/SUR2B inhibitors. This screen identified several novel classes of Kir6.1/SUR2B inhibitors, including the first potent (IC50 ~100 nM) and selective inhibitor published to date, termed VU0542270. Here, we expand on this work by disclosing the identity and pharmacological properties of four additional Kir6.1/SUR2B inhibitors that are structurally unrelated to Kir to VU0542270. These inhibitors, named VU0212387, VU0543336, VU0605768, and VU0544086, inhibit Kir6.1/SUR2B with IC50 values ranging from approximately 100 nM to 1 µM and exhibit no apparent inhibitory activity toward Kir6.2/SUR1. Functional analysis of heterologously expressed subunit combinations of Kir6.1, Kir6.2, SUR1, SUR2A, and SUR2B and demonstrated that all four inhibitors act on SUR2 to induce channel inhibition. Interestingly, VU0543336 and VU0212387 exhibit paradoxical stimulatory effects on Kir6.2/SUR1 at higher doses. This study broadens our understanding of KATP channel pharmacology, generally, and reveals novel chemical matter for the development of Kir6.1/SUR2-selective drugs, specifically.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"18 1","pages":"2398565"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302304","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

Dynamic duo: Kir6 and SUR in K_ATP channel structure and function. 动态二重奏：KATP 通道结构和功能中的 Kir6 和 SUR。

Channels (Austin, Tex.) Pub Date : 2024-12-01 Epub Date: 2024-03-15 DOI: 10.1080/19336950.2024.2327708

Bruce L Patton, Phillip Zhu, Assmaa ElSheikh, Camden M Driggers, Show-Ling Shyng

引用次数: 0

Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes. naïve小鼠背根神经节神经元的钠电流:性别间无显著差异。

Channels (Austin, Tex.) Pub Date : 2024-12-01 Epub Date: 2023-12-06 DOI: 10.1080/19336950.2023.2289256

Mohammad-Reza Ghovanloo, Sidharth Tyagi, Peng Zhao, Philip R Effraim, Sulayman D Dib-Hajj, Stephen G Waxman

{"title":"Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes.","authors":"Mohammad-Reza Ghovanloo, Sidharth Tyagi, Peng Zhao, Philip R Effraim, Sulayman D Dib-Hajj, Stephen G Waxman","doi":"10.1080/19336950.2023.2289256","DOIUrl":"10.1080/19336950.2023.2289256","url":null,"abstract":"Sexual dimorphism has been reported in multiple pre-clinical and clinical studies on pain. Previous investigations have suggested that in at least some states, rodent dorsal root ganglion (DRG) neurons display differential sex-dependent regulation and expression patterns of various proteins involved in the pain pathway. Our goal in this study was to determine whether sexual dimorphism in the biophysical properties of voltage-gated sodium (Nav) currents contributes to these observations in rodents. We recently developed a novel method that enables high-throughput, unbiased, and automated functional analysis of native rodent sensory neurons from naïve WT mice profiled simultaneously under uniform experimental conditions. In our previous study, we performed all experiments in neurons that were obtained from mixed populations of adult males or females, which were combined into single (combined male/female) data sets. Here, we have re-analyzed the same previously published data and segregated the cells based on sex. Although the number of cells in our previously published data sets were uneven for some comparisons, our results do not show sex-dependent differences in the biophysical properties of Nav currents in these native DRG neurons.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"18 1","pages":"2289256"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500362","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

Transient receptor potential vanilloid type 1: cardioprotective effects in diabetic models. 瞬时受体电位1型香草素:糖尿病模型中的心脏保护作用。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-11-20 DOI: 10.1080/19336950.2023.2281743

Jiaqi Bao, Zhicheng Gao, Yilan Hu, Lifang Ye, Lihong Wang

{"title":"Transient receptor potential vanilloid type 1: cardioprotective effects in diabetic models.","authors":"Jiaqi Bao, Zhicheng Gao, Yilan Hu, Lifang Ye, Lihong Wang","doi":"10.1080/19336950.2023.2281743","DOIUrl":"10.1080/19336950.2023.2281743","url":null,"abstract":"Cardiovascular disease, especially heart failure (HF) is the leading cause of death in patients with diabetes. Individuals with diabetes are prone to a special type of cardiomyopathy called diabetic cardiomyopathy (DCM), which cannot be explained by heart diseases such as hypertension or coronary artery disease, and can contribute to HF. Unfortunately, the current treatment strategy for diabetes-related cardiovascular complications is mainly to control blood glucose levels; nonetheless, the improvement of cardiac structure and function is not ideal. The transient receptor potential cation channel subfamily V member 1 (TRPV1), a nonselective cation channel, has been shown to be universally expressed in the cardiovascular system. Increasing evidence has shown that the activation of TRPV1 channel has a potential protective influence on the cardiovascular system. Numerous studies show that activating TRPV1 channels can improve the occurrence and progression of diabetes-related complications, including cardiomyopathy; however, the specific mechanisms and effects are unclear. In this review, we summarize that TRPV1 channel activation plays a protective role in the heart of diabetic models from oxidation/nitrification stress, mitochondrial function, endothelial function, inflammation, and cardiac energy metabolism to inhibit the occurrence and progression of DCM. Therefore, TRPV1 may become a latent target for the prevention and treatment of diabetes-induced cardiovascular complications.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"17 1","pages":"2281743"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138178171","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

Fibrillin-1 mutation contributes to Marfan syndrome by inhibiting Cav1.2-mediated cell proliferation in vascular smooth muscle cells. 纤颤蛋白1突变通过抑制血管平滑肌细胞中cav1.2介导的细胞增殖而导致马凡氏综合征。

Channels (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19336950.2023.2192377

Wenfeng Lin, Jiaqi Xiong, Yefan Jiang, Hao Liu, Jinhui Bian, Juejin Wang, Yongfeng Shao, Buqing Ni

{"title":"Fibrillin-1 mutation contributes to Marfan syndrome by inhibiting Cav1.2-mediated cell proliferation in vascular smooth muscle cells.","authors":"Wenfeng Lin, Jiaqi Xiong, Yefan Jiang, Hao Liu, Jinhui Bian, Juejin Wang, Yongfeng Shao, Buqing Ni","doi":"10.1080/19336950.2023.2192377","DOIUrl":"10.1080/19336950.2023.2192377","url":null,"abstract":"Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutation in fibrillin-1 (FBN1). However, the molecular mechanism underlying MFS remains poorly understood. The study aimed to explore how the L-type calcium channel (CaV1.2) modulates disease progression of MFS and to identify a potential effective target for attenuating MFS. KEGG enrichment analysis showed that the calcium signaling pathway gene set was significantly enriched. We demonstrated that FBN1 deficiency exhibited inhibition on both the expression of Cav1.2 and proliferation of vascular smooth muscle cells (VSMCs). Then, we examined whether FBN1 mediates Cav1.2 via regulating TGF-β1. Higher levels of TGF-β1 were observed in the serum and aortic tissues from patients with MFS. TGF-β1 modulated Cav1.2 expression in a concentration-dependent manner. We evaluated the role of Cav1.2 in MFS by small interfering RNA and Cav1.2 agonist Bay K8644. The effect of Cav1.2 on cell proliferation was dependent on c-Fos activity. These results demonstrated FBN1 deficiency decreased the expression levels of Cav1.2 via regulation of TGF-β1, and downregulation of Cav1.2 inhibited cell proliferation of human aortic smooth muscle cells (HASMCs) in MFS patients. These findings suggest that Cav1.2 may be an appealing therapeutic target for MFS.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"17 1","pages":"2192377"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9567567","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

The role of ATP binding cassette (ABC) transporters in breast cancer: Evaluating prognosis, predicting immunity, and guiding treatment. ATP结合盒（ABC）转运蛋白在癌症中的作用：评估预后、预测免疫力和指导治疗。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-31 DOI: 10.1080/19336950.2023.2273247

Yuan Yuan, Zhouhong Xiang, Yuhua Xia, Jiaheng Xie, Xiudi Jiang, Zhicheng Lu

{"title":"The role of ATP binding cassette (ABC) transporters in breast cancer: Evaluating prognosis, predicting immunity, and guiding treatment.","authors":"Yuan Yuan, Zhouhong Xiang, Yuhua Xia, Jiaheng Xie, Xiudi Jiang, Zhicheng Lu","doi":"10.1080/19336950.2023.2273247","DOIUrl":"10.1080/19336950.2023.2273247","url":null,"abstract":"Breast cancer is currently the most prevalent form of cancer worldwide. Nevertheless, there remains limited clarity regarding our understanding of the tumor microenvironment and metabolic characteristics associated with it. ATP-binding cassette (ABC) transporters are the predominant transmembrane transporters found in organisms. Therefore, it is essential to investigate the role of ABC transporters in breast cancer. Transcriptome data from breast cancer patients were downloaded from the TCGA database. ABC transporter-related genes were obtained from the Genecards database. By LASSO regression, ABC-associated prognostic signature was constructed in breast cancer. Subsequently, immune microenvironment analysis was performed. Finally, cell experiments were performed to verify the function of ABCB7 in the breast cancer cell lines MDA-MB-231 and MCF-7. Using the ABC transporter-associated signature, we calculated a risk score for each breast cancer patient. Patients with breast cancer were subsequently categorized into high-risk and low-risk groups, utilizing the median risk score as the threshold. Notably, patients in the high-risk group exhibited significantly worse prognosis (P<0.05). Additionally, differences were observed in terms of immune cell infiltration levels, immune correlations, and gene expression of immune checkpoints between the two groups. Functional experiments conducted on breast cancer cell lines MDA-MB-231 and MCF-7 demonstrated that ABCB7 knockdown significantly diminished cell activity, proliferation, invasion, and migration. These findings emphasize the significance of understanding ABC transporter-mediated metabolic and transport characteristics in breast cancer, offering promising directions for further research and potential therapeutic interventions.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"17 1","pages":"2273247"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415686","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

Type 3 IP3 receptor: Its structure, functions, and related disease implications. 3型IP3受体：其结构、功能和相关疾病的意义。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-11 DOI: 10.1080/19336950.2023.2267416

Lvying Wu, Jin Chen

引用次数: 0