Channels (Austin, Tex.)最新文献_第9页

Spinal AMPA receptors: Amenable players in central sensitization for chronic pain therapy? 脊髓 AMPA 受体：用于慢性疼痛治疗的中枢敏化作用？

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1885836

Olga Kopach, Nana Voitenko

引用次数: 0

Nitrergic modulation of ion channel function in regulating neuronal excitability. 离子通道在神经元兴奋性调节中的氮调节作用。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.2002594

Jereme G Spiers, Joern R Steinert

{"title":"Nitrergic modulation of ion channel function in regulating neuronal excitability.","authors":"Jereme G Spiers, Joern R Steinert","doi":"10.1080/19336950.2021.2002594","DOIUrl":"https://doi.org/10.1080/19336950.2021.2002594","url":null,"abstract":"Nitric oxide (NO) signaling in the brain provides a wide range of functional properties in response to neuronal activity. NO exerts its effects through different signaling pathways, namely, through the canonical soluble guanylyl cyclase-mediated cGMP production route and via post-translational protein modifications. The latter pathways comprise cysteine S-nitrosylation and 3-nitrotyrosination of distinct tyrosine residues. Many ion channels are targeted by one or more of these signaling routes, which leads to their functional regulation under physiological conditions or facilities their dysfunction leading to channelopathies in many pathologies. The resulting alterations in ion channel function changes neuronal excitability, synaptic transmission, and action potential propagation. Transient and activity-dependent NO production mediates reversible ion channel modifications via cGMP and S-nitrosylation signaling, whereas more pronounced and longer-term NO production during conditions of elevated oxidative stress leads to increasingly cumulative and irreversible protein 3-nitrotyrosination. The complexity of this regulation and vast variety of target ion channels and their associated functional alterations presents a challenging task in assessing and understanding the role of NO signaling in physiology and disease.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"666-679"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39895645","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

PANX1 is a potential prognostic biomarker associated with immune infiltration in pancreatic adenocarcinoma: A pan-cancer analysis. PANX1是与胰腺腺癌免疫浸润相关的潜在预后生物标志物:一项泛癌分析。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.2004758

Lingling Bao, Kai Sun, Xuede Zhang

{"title":"PANX1 is a potential prognostic biomarker associated with immune infiltration in pancreatic adenocarcinoma: A pan-cancer analysis.","authors":"Lingling Bao, Kai Sun, Xuede Zhang","doi":"10.1080/19336950.2021.2004758","DOIUrl":"https://doi.org/10.1080/19336950.2021.2004758","url":null,"abstract":"Pannexin 1 (PANX1) channel is a critical ATP-releasing pathway that modulates tumor immunity, progression, and prognosis. However, the roles of PANX1 in different cancers remain unclear. We analyzed the expression of PANX1 in human pan-cancer in the Oncomine and GEPIA2.0 databases. The prognostic value of PANX1 expression was determined using Kaplan-Meier plotter and OncoLnc tools. The correlation between PANX1 and tumor-infiltrating immune cells was investigated using the TIMER 2.0. In addition, the relationship between PANX1 and immunomodulators was explored using TISIDB. Finally, gene set enrichment analysis (GSEA) was performed utilizing LinkedOmics. The results indicated that PANX1 was overexpressed in most cancers compared to normal tissues. The high expression of PANX1 was associated with poor prognosis in multiple tumors, especially in pancreatic adenocarcinoma (PAAD). In addition, PANX1 was correlated with a variety of immunomodulators, such as CD274, IL10, CD276, IL2RA, TAP1, and TAP2. PANX1 expression level was significantly related to infiltration of multiple immune cells in many cancers, including cancer associated fibroblast, macrophage, and neutrophil cells. Further analysis revealed that PANX1 was significantly associated with T cells CD8+ (rho = 0.524, P = 1.94e-13) and Myeloid dendritic cell (rho = 0.564, P = 9.45e-16). GSEA results showed that PANX1 was closely associated with leukocyte cell-cell adhesion, endoplasmic reticulum lumen, ECM-receptor interaction, and Focal adhesion pathways in PAAD. PANX1 expression was higher in pan-cancer samples than in normal tissues. The high expression of PANX1 was associated with poor outcome and immune infiltration in multiple cancers, especially in PAAD.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"680-696"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39726949","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

Differential expression of GluN2 NMDA receptor subunits in the dorsal horn of male and female rats. GluN2 NMDA受体亚基在雌雄大鼠背角的差异表达。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1871205

Santa Temi, Christopher Rudyk, Jennifer Armstrong, Jeffrey A Landrigan, Chris Dedek, Natalina Salmaso, Michael E Hildebrand

{"title":"Differential expression of GluN2 NMDA receptor subunits in the dorsal horn of male and female rats.","authors":"Santa Temi, Christopher Rudyk, Jennifer Armstrong, Jeffrey A Landrigan, Chris Dedek, Natalina Salmaso, Michael E Hildebrand","doi":"10.1080/19336950.2020.1871205","DOIUrl":"10.1080/19336950.2020.1871205","url":null,"abstract":"N-methyl-D-aspartate receptors (NMDARs) are excitatory ionotropic glutamate receptors expressed throughout the CNS, including in the spinal dorsal horn. The GluN2 subtypes of NMDAR subunit, which include GluN2A, GluN2B, and GluN2D in the dorsal horn, confer NMDARs with structural and functional variability, enabling heterogeneity in synaptic transmission and plasticity. Despite essential roles for NMDARs in physiological and pathological pain processing, the distribution and function of these specific GluN2 isoforms across dorsal horn laminae remain poorly understood. Surprisingly, there is a complete lack of knowledge of GluN2 expression in female rodents. We, therefore, investigated the relative expression of specific GluN2 variants in the dorsal horn of lumbar (L4/L5) spinal cord from both male and female rats. In order to detect synaptic GluN2 isoforms, we used pepsin antigen-retrieval to unmask these highly cross-linked protein complexes. We found that GluN2B and GluN2D are preferentially localized to the pain-processing superficial regions of the dorsal horn in males, while only GluN2B is predominantly localized to the superficial dorsal horn of female rats. The GluN2A subunit is diffusely localized to neuropil throughout the dorsal horn of both males and females, while GluN2B and GluN2D immunolabelling are found both in the neuropil and on the soma of dorsal horn neurons. Finally, we identified an unexpected enhanced expression of GluN2B in the medial division of the superficial dorsal horn, but in males only. These sex-specific localization patterns of GluN2-NMDAR subunits across dorsal horn laminae have significant implications for the understanding of divergent spinal mechanisms of pain processing.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"179-192"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38872074","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

Selective Targeting of Nav1.7 with Engineered Spider Venom-Based Peptides. 用基于蜘蛛毒液的工程肽选择性靶向 Nav1.7。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1860382

Robert A Neff, Alan D Wickenden

引用次数: 0

More than a pore: How voltage-gated calcium channels act on different levels of neuronal communication regulation. 超过一个孔:电压门控钙通道如何作用于不同水平的神经元通讯调节。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1900024

Jennifer Heck, Ana Carolina Palmeira Do Amaral, Stephan Weißbach, Abderazzaq El Khallouqi, Arthur Bikbaev, Martin Heine

{"title":"More than a pore: How voltage-gated calcium channels act on different levels of neuronal communication regulation.","authors":"Jennifer Heck, Ana Carolina Palmeira Do Amaral, Stephan Weißbach, Abderazzaq El Khallouqi, Arthur Bikbaev, Martin Heine","doi":"10.1080/19336950.2021.1900024","DOIUrl":"10.1080/19336950.2021.1900024","url":null,"abstract":"Voltage-gated calcium channels (VGCCs) represent key regulators of the calcium influx through the plasma membrane of excitable cells, like neurons. Activated by the depolarization of the membrane, the opening of VGCCs induces very transient and local changes in the intracellular calcium concentration, known as calcium nanodomains, that in turn trigger calcium-dependent signaling cascades and the release of chemical neurotransmitters. Based on their central importance as concierges of excitation-secretion coupling and therefore neuronal communication, VGCCs have been studied in multiple aspects of neuronal function and malfunction. However, studies on molecular interaction partners and recent progress in omics technologies have extended the actual concept of these molecules. With this review, we want to illustrate some new perspectives of VGCCs reaching beyond their function as calcium-permeable pores in the plasma membrane. Therefore, we will discuss the relevance of VGCCs as voltage sensors in functional complexes with ryanodine receptors, channel-independent actions of auxiliary VGCC subunits, and provide an insight into how VGCCs even directly participate in gene regulation. Furthermore, we will illustrate how structural changes in the intracellular C-terminus of VGCCs generated by alternative splicing events might not only affect the biophysical channel characteristics but rather determine their molecular environment and downstream signaling pathways.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"322-338"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38998362","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

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