Channels (Austin, Tex.)最新文献_第10页

Functional modulation of the human voltage-gated sodium channel Na_V1.8 by auxiliary β subunits. 辅助 β 亚基对人类电压门控钠通道 NaV1.8 的功能调节。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1860399

S T Nevin, N Lawrence, A Nicke, R J Lewis, D J Adams

{"title":"Functional modulation of the human voltage-gated sodium channel NaV1.8 by auxiliary β subunits.","authors":"S T Nevin, N Lawrence, A Nicke, R J Lewis, D J Adams","doi":"10.1080/19336950.2020.1860399","DOIUrl":"10.1080/19336950.2020.1860399","url":null,"abstract":"The voltage-gated sodium channel Nav1.8 mediates the tetrodotoxin-resistant (TTX-R) Na+ current in nociceptive primary sensory neurons, which has an important role in the transmission of painful stimuli. Here, we describe the functional modulation of the human Nav1.8 α-subunit in Xenopus oocytes by auxiliary β subunits. We found that the β3 subunit down-regulated the maximal Na+ current amplitude and decelerated recovery from inactivation of hNav1.8, whereas the β1 and β2 subunits had no such effects. The specific regulation of Nav1.8 by the β3 subunit constitutes a potential novel regulatory mechanism of the TTX-R Na+ current in primary sensory neurons with potential implications in chronic pain states. In particular, neuropathic pain states are characterized by a down-regulation of Nav1.8 accompanied by increased expression of the β3 subunit. Our results suggest that these two phenomena may be correlated, and that increased levels of the β3 subunit may directly contribute to the down-regulation of Nav1.8. To determine which domain of the β3 subunit is responsible for the specific regulation of hNav1.8, we created chimeras of the β1 and β3 subunits and co-expressed them with the hNav1.8 α-subunit in Xenopus oocytes. The intracellular domain of the β3 subunit was shown to be responsible for the down-regulation of maximal Nav1.8 current amplitudes. In contrast, the extracellular domain mediated the effect of the β3 subunit on hNav1.8 recovery kinetics.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"79-93"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38369854","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

A pan-cancer analysis revealed the role of the SLC16 family in cancer. 一项泛癌症分析揭示了SLC16家族在癌症中的作用。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1965422

Jun Li, Jiaheng Xie, Dan Wu, Liang Chen, Zetian Gong, Rui Wu, Yiming Hu, Jiangning Zhao, Yetao Xu

引用次数: 16

Solute carrier transporter superfamily member SLC16A1 is a potential prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma. 溶质载体转运体超家族成员 SLC16A1 是一种潜在的预后生物标志物，并与皮肤黑色素瘤的免疫浸润有关。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1953322

Jiaheng Xie, Zhechen Zhu, Yuan Cao, Shujie Ruan, Ming Wang, Jingping Shi

{"title":"Solute carrier transporter superfamily member SLC16A1 is a potential prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma.","authors":"Jiaheng Xie, Zhechen Zhu, Yuan Cao, Shujie Ruan, Ming Wang, Jingping Shi","doi":"10.1080/19336950.2021.1953322","DOIUrl":"10.1080/19336950.2021.1953322","url":null,"abstract":"Melanoma is a type of cancer with a relatively poor prognosis. The development of immunotherapy for the treatment of patients with melanoma has drawn considerable attention in recent years. It is of great clinical significance to identify novel promising prognostic biomarkers and to explore their roles in the immune microenvironment. The solute carrier (SLC) superfamily is a group of transporters predominantly expressed on the cell membrane and are involved in substance transport. SLC16A1 is a member of the SLC family, participating in the transport of lactate, pyruvate, amino acids, ketone bodies, etc. The role of SLC16A1 in tumor immunity has been recently elucidated, while its role in melanoma remains unclear. In this study, bioinformatics analysis was performed to explore the role of SLC16A1 in melanoma. The results showed that high SLC16A1 expression was correlated with decreased overall survival in patients with melanoma. The genes co-expressed with SLC16A1 were significantly enriched in metabolic regulation, protein ubiquitination, and substance localization. Moreover, SLC16A1 was correlated with the infiltration of immune cells. In conclusion, SLC16A1 is a robust prognostic biomarker for melanoma and may be used as a novel target in immunotherapy.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"483-495"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/07/KCHL_15_1953322.PMC8279094.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39178900","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 clinical and genetic heterogeneity analysis of five families with primary periodic paralysis. 五个原发性周期性麻痹家族的临床和遗传异质性分析。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1857980

Quanquan Wang, Zhe Zhao, Hongrui Shen, Qi Bing, Nan Li, Jing Hu

{"title":"The clinical and genetic heterogeneity analysis of five families with primary periodic paralysis.","authors":"Quanquan Wang, Zhe Zhao, Hongrui Shen, Qi Bing, Nan Li, Jing Hu","doi":"10.1080/19336950.2020.1857980","DOIUrl":"10.1080/19336950.2020.1857980","url":null,"abstract":"To explore the clinical and genetic characteristics of five families with primary periodic paralysis (PPP). We reviewed clinical manifestations, laboratory results, electrocardiogram, electromyography, muscle biopsy, and genetic analysis from five families with PPP. Five families with PPP included: hypokalemic periodic paralysis type 1 (HypoPP1, CACNA1S, 1/5), hypokalemic periodic paralysis type 2 (HypoPP2, SCN4A, 2/5), normokalemic periodic paralysis (NormoPP, SCN4A, 1/5), and Andersen-Tawil syndrome (ATS, KCNJ2, 1/5). The basic clinical manifestations of five families were consistent with PPP, presenting with paroxysmal muscle weakness, with or without abnormal serum potassium. ATS was accompanied by ventricular arrhythmias, and skeletal and craniofacial anomalies, developing with a permanent fixed myopathy later. The electromyography showed diffuse myopathic discharge, and muscle biopsy showed tubular aggregates. Genetic testing revealed five families with PPP carried CACNA1S (R1242S), SCN4A (R675Q, T704M), and KCNJ2 (R218Q) respectively. The novel heterozygous R1242S mutation in CACNA1S caused a conformational change in the protein structure, and the amino acid of this mutation site was highly conserved among different species. SCN4A mutations led to two phenotypes of HypoPP2 and NormoPP. PPPs are autosomal dominant disorders of ion channel dysfunction characterized by episodic flaccid muscle weakness secondary to abnormal sarcolemmal excitability. PPPs are caused by mutations in skeletal muscle calcium channel CaV1.1 gene (CACNA1S), sodium channel NaV1.4 gene (SCN4A), and potassium channels Kir2.1, Kir3.4 genes (KCNJ2, KCNJ5), including HypoPP1, HypoPP2, NormoPP, HyperPP, and ATS, which have significant clinical and genetic heterogeneity. Diagnosis is based on the characteristic clinical presentation then confirmed by genetic testing.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"20-30"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38738679","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

Potassium channels as molecular targets of endocannabinoids. 作为内大麻素分子靶点的钾通道。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1910461

Yu-Fung Lin

{"title":"Potassium channels as molecular targets of endocannabinoids.","authors":"Yu-Fung Lin","doi":"10.1080/19336950.2021.1910461","DOIUrl":"10.1080/19336950.2021.1910461","url":null,"abstract":"Endocannabinoids are a group of endogenous mediators derived from membrane lipids, which are implicated in a wide variety of physiological functions such as blood pressure regulation, immunity, pain, memory, reward, perception, reproduction, and sleep. N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) represent two major endocannabinoids in the human body and they exert many of their cellular and organ system effects by activating the Gi/o protein-coupled, cannabinoid type 1 (CB1) and type 2 (CB2) receptors. However, not all effects of cannabinoids are ascribable to their interaction with CB1 and CB2 receptors; indeed, macromolecules like other types of receptors, ion channels, transcription factors, enzymes, transporters, and cellular structure have been suggested to mediate the functional effects of cannabinoids. Among the proposed molecular targets of endocannabinoids, potassium channels constitute an intriguing group, because these channels not only are crucial in shaping action potentials and controlling the membrane potential and cell excitability, thereby regulating a wide array of physiological processes, but also serve as potential therapeutic targets for the treatment of cancer and metabolic, neurological and cardiovascular disorders. This review sought to survey evidence pertaining to the CB1 and CB2 receptor-independent actions of endocannabinoids on ion channels, with an emphasis on AEA and potassium channels. To better understand the functional roles as well as potential medicinal uses of cannabinoids in human health and disease, further mechanistic studies to delineate interactions between various types of cannabinoids and ion channels, including members in the potassium channel superfamily, are warranted.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"408-423"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39201623","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

Expression defect of the rare variant/Brugada mutation R1512W depends upon the SCN5A splice variant background and can be rescued by mexiletine and the common polymorphism H558R. 罕见变异/布鲁加达突变 R1512W 的表达缺陷取决于 SCN5A 剪接变异背景，并可被 mexiletine 和常见多态性 H558R 挽救。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1875645

Rou-Mu Hu, Evelyn J Song, David J Tester, Isabelle Deschenes, Michael J Ackerman, Jonathan C Makielski, Bi-Hua Tan

{"title":"Expression defect of the rare variant/Brugada mutation R1512W depends upon the SCN5A splice variant background and can be rescued by mexiletine and the common polymorphism H558R.","authors":"Rou-Mu Hu, Evelyn J Song, David J Tester, Isabelle Deschenes, Michael J Ackerman, Jonathan C Makielski, Bi-Hua Tan","doi":"10.1080/19336950.2021.1875645","DOIUrl":"10.1080/19336950.2021.1875645","url":null,"abstract":"Background : Mutations in SCN5A that decrease Na current underlie arrhythmia syndromes such as the Brugada syndrome (BrS). SCN5A in humans has two splice variants, one lacking a glutamine at position 1077 (Q1077del) and one containing Q1077. We investigated the effect of splice variant background on loss-of-function and rescue for R1512W, a mutation reported to cause BrS. Methods and results : We made the mutation in both variants and expressed them in HEK-293 cells for voltage-clamp study. After 24 hours of transfection, the current expression level of R1512W was reduced by ~50% in both Q1077del and Q1077 compared to the wild-type (WT) channel, respectively. The activation and inactivation midpoint were not different between WT and mutant channels in both splice variant backgrounds. However, slower time constants of recovery and enhanced intermediate inactivation were observed for R1512W/Q1077 compared with WT-Q1077, while the recovery and intermediate inactivation parameters of R1512W/Q1077del were similar to WT-Q1077del. Furthermore, both mexiletine and the common polymorphism H558R restored peak sodium current (INa) amplitude of the mutant channel by increasing the cell surface expression of SCN5A. Conclusion : These findings provide further evidence that the splice variant affects the molecular phenotype with implications for the clinical phenotype, and they provide insight into the expression defect mechanisms and potential treatment in BrS.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"253-261"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25328840","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

TRPV1 channels as a newly identified target for vitamin D. TRPV1 通道是新发现的维生素 D 靶点。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1905248

Wentong Long, Janyne Johnson, Subha Kalyaanamoorthy, Peter Light

{"title":"TRPV1 channels as a newly identified target for vitamin D.","authors":"Wentong Long, Janyne Johnson, Subha Kalyaanamoorthy, Peter Light","doi":"10.1080/19336950.2021.1905248","DOIUrl":"10.1080/19336950.2021.1905248","url":null,"abstract":"Vitamin D is known to elicit many biological effects in diverse tissue types and is thought to act almost exclusively upon its canonical receptor within the nucleus, leading to gene transcriptional changes and the subsequent cellular response. However, not all the observed effects of vitamin D can be attributed to this sole mechanism, and other cellular targets likely exist but remain to be identified. Our recent discovery that vitamin D is a partial agonist of the Transient Receptor Potential Vanilloid family 1 (TRPV1) channel may provide new insights as to how this important vitamin exerts its biological effects either independently or in addition to the nuclear vitamin D receptor. In this review, we discuss the literature surrounding this apparent discrepancy in vitamin D signaling and compare vitamin D with known TRPV1 ligands with respect to their binding to TRPV1. Furthermore, we provide evidence supporting the notion that this novel vitamin D/TRPV1 axis may explain some of the beneficial actions of this vitamin in disease states where TRPV1 expression and vitamin D deficiency are known to overlap. Finally, we discuss whether vitamin D may also act on other members of the TRP family of ion channels.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"15 1","pages":"360-374"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10296011","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

17β-Estradiol activates Cl^- channels via the estrogen receptor α pathway in human thyroid cells. 17β-雌二醇通过雌激素受体α途径激活人甲状腺细胞中的Cl-通道。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1957627

Meisheng Yu, Yuan Wei, Yanfang Zheng, Lili Yang, Long Meng, Jiawei Lin, Peisheng Xu, Sanaa Ahmed Nagi Abdu Mahdy, Linyan Zhu, Shuang Peng, Lixin Chen, Liwei Wang

{"title":"17β-Estradiol activates Cl- channels via the estrogen receptor α pathway in human thyroid cells.","authors":"Meisheng Yu, Yuan Wei, Yanfang Zheng, Lili Yang, Long Meng, Jiawei Lin, Peisheng Xu, Sanaa Ahmed Nagi Abdu Mahdy, Linyan Zhu, Shuang Peng, Lixin Chen, Liwei Wang","doi":"10.1080/19336950.2021.1957627","DOIUrl":"https://doi.org/10.1080/19336950.2021.1957627","url":null,"abstract":"Estradiol regulates thyroid function, and chloride channels are involved in the regulation of thyroid function. However, little is known about the role of chloride channels in the regulation of thyroid functions by estrogen. In this study, the effects of estrogen on chloride channel activities in human thyroid Nthy-ori3-1 cells were therefore investigated using the whole cell patch-clamp technique. The results showed that the extracellular application of 17β-estradiol (E2) activated Cl- currents, which reversed at a potential close to Cl- equilibrium potential and showed remarkable outward rectification and an anion permeability of I- > Br- > Cl- > gluconate. The Cl- currents were inhibited by the chloride channel blockers, NPPB and tamoxifen. Quantitative Real-time PCR results demonstrated that ClC-3 expression was highest in ClC family member in Nthy-ori3-1 cells. The down-regulation of ClC-3 expression by ClC-3 siRNA inhibited E2-induced Cl- current. The Cl- current was blocked by the estrogen receptor antagonist, ICI 182780 (fulvestrant). Estrogen receptor alpha (ERα) and not estrogen receptor beta was the protein expressed in Nthy-ori3-1 cells, and the knockdown of ERα expression with ERα siRNA abolished E2-induced Cl- currents. Estradiol can promote the accumulation of ClC-3 in cell membrane. ERα and ClC-3 proteins were partially co-localized in the cell membrane of Nthy-ori3-1 cells after estrogen exposure. The results suggest that estrogen activates chloride channels via ERα in normal human thyroid cells, and ClC-3 proteins play a pivotal role in the activation of E2-induced Cl- current.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"516-527"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39341917","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 channels: A Global Bibliometric analysis From 2012 to 2021. 瞬时受体电位通道:2012 - 2021年全球文献计量学分析。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1983100

Xueping Zhu, Chuanxi Tian, Yan Zhou, Jingjing Shi, Guozhen Yuan, Limei Zhang, Yuchen Jiang, Wenjing Xue, Yihang Du, Yuanhui Hu

{"title":"Transient Receptor Potential channels: A Global Bibliometric analysis From 2012 to 2021.","authors":"Xueping Zhu, Chuanxi Tian, Yan Zhou, Jingjing Shi, Guozhen Yuan, Limei Zhang, Yuchen Jiang, Wenjing Xue, Yihang Du, Yuanhui Hu","doi":"10.1080/19336950.2021.1983100","DOIUrl":"https://doi.org/10.1080/19336950.2021.1983100","url":null,"abstract":"The transient receptor potential (TRP) channels, nonselective ion channels, mediate the fluxes of various types of cations across the cell membrane such as Na+, K+, Mg2+, and Ca2 + . TRPA (Ankyrin), TRPC (Canonical), TRPM (Melastatin), TRPV (Vanilloid), TRPP (Polycystin), and TRPML (Mucolipin) are TRP major families members. These channels play essential roles in diverse physiologic processes, and participate in virtually every sensory modality. TRPs can be activated by chemicals, temperature, stretch/pressure, osmolarity, pH, and so on, and play a major role in the five primary senses, such as vision, taste, hearing, smell, and touch. In recent years, TRP channels are widely studied in the field of nervous, intestinal, renal, urogenital, respiratory, and cardiovascular systems in diverse therapeutic areas including pain and itch, headache, pulmonary function, oncology, neurology, visceral organs, and genetic diseases [1]. Bibliometric analysis has been widely used to calculate the productivity of countries, institutions, authors, and the frequency of keywords to explore research hotspots/frontiers in specific fields [2–4]. In the present study, we performed a bibliometric analysis to systematically evaluate the TRP channels studies from 2012 to 2021 by CiteSpace and VOSviewer to provide researchers with some direction regarding TRP channels research [5,6]. Data source and search","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"624-634"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39625007","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

Regulation of acid-sensing ion channels by protein binding partners. 蛋白质结合伙伴对酸敏感离子通道的调节。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1976946

Megan M Cullinan, Robert C Klipp, John R Bankston

引用次数: 7