Channels (Austin, Tex.)最新文献_第9页

Kv1.3 inhibition attenuates neuroinflammation through disruption of microglial calcium signaling. 抑制 Kv1.3 可通过破坏小胶质细胞的钙信号转导减轻神经炎症。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1853943

Alla F Fomina, Hai M Nguyen, Heike Wulff

引用次数: 0

The resting membrane potential of hSC-CM in a syncytium is more hyperpolarised than that of isolated cells. 合胞体中hSC CM的静息膜电位比分离细胞的静息膜电势更为超极化。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1871815

Dieter V Van de Sande, Ivan Kopljar, Alaerts Maaike, Ard Teisman, David J Gallacher, Loeys Bart, Dirk J Snyders, Luc Leybaert, Hua Rong Lu, Alain J Labro

{"title":"The resting membrane potential of hSC-CM in a syncytium is more hyperpolarised than that of isolated cells.","authors":"Dieter V Van de Sande, Ivan Kopljar, Alaerts Maaike, Ard Teisman, David J Gallacher, Loeys Bart, Dirk J Snyders, Luc Leybaert, Hua Rong Lu, Alain J Labro","doi":"10.1080/19336950.2021.1871815","DOIUrl":"10.1080/19336950.2021.1871815","url":null,"abstract":"Human-induced pluripotent stem cell (hiPSC) and stem cell (hSC) derived cardiomyocytes (CM) are gaining popularity as in vitro model for cardiology and pharmacology studies. A remaining flaw of these cells, as shown by single-cell electrophysiological characterization, is a more depolarized resting membrane potential (RMP) compared to native CM. Most reports attribute this to a lower expression of the Kir2.1 potassium channel that generates the IK1 current. However, most RMP recordings are obtained from isolated hSC/hiPSC-CMs whereas in a more native setting these cells are interconnected with neighboring cells by connexin-based gap junctions, forming a syncytium. Hereby, these cells are electrically connected and the total pool of IK1 increases. Therefore, the input resistance (Ri) of interconnected cells is lower than that of isolated cells. During patch clamp experiments pipettes need to be well attached or sealed to the cell, which is reflected in the seal resistance (Rs), because a nonspecific ionic current can leak through this pipette-cell contact or seal and balance out small currents within the cell such as IK1. By recording the action potential of isolated hSC-CMs and that of hSC-CMs cultured in small monolayers, we show that the RMP of hSC-CMs in monolayer is approximately -20 mV more hyperpolarized compared to isolated cells. Accordingly, adding carbenoxolone, a connexin channel blocker, isolates the cell that is patch clamped from its neighboring cells of the monolayer and depolarizes the RMP. The presented data show that the recorded RMP of hSC-CMs in a syncytium is more negative than that determined from isolated hSC/hiPSC-CMs, most likely because the active pool of Kir2.1 channels increased.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"239-252"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38834332","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

Quantitative roles of ion channel dynamics on ventricular action potential. 离子通道动力学对心室动作电位的定量作用

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1940628

Ahmet Kürşad Sırcan, Sevgi Şengül Ayan

引用次数: 0

The focal adhesion protein Testin modulates KCNE2 potassium channel β subunit activity. 病灶粘附蛋白Testin可调节KCNE2钾离子通道β亚基的活性。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1874119

Maria Papanikolaou, Shawn M Crump, Geoffrey W Abbott

{"title":"The focal adhesion protein Testin modulates KCNE2 potassium channel β subunit activity.","authors":"Maria Papanikolaou, Shawn M Crump, Geoffrey W Abbott","doi":"10.1080/19336950.2021.1874119","DOIUrl":"10.1080/19336950.2021.1874119","url":null,"abstract":"Coronary Artery Disease (CAD) typically kills more people globally each year than any other single cause of death. A better understanding of genetic predisposition to CAD and the underlying mechanisms will help to identify those most at risk and contribute to improved therapeutic approaches. KCNE2 is a functionally versatile, ubiquitously expressed potassium channel β subunit associated with CAD and cardiac arrhythmia susceptibility in humans and mice. Here, to identify novel KCNE2 interaction partners, we employed yeast two-hybrid screening of adult and fetal human heart libraries using the KCNE2 intracellular C-terminal domain as bait. Testin (encoded by TES), an endothelial cell-expressed, CAD-associated, focal adhesion protein, was identified as a high-confidence interaction partner for KCNE2. We confirmed physical association between KCNE2 and Testin in vitro by co-immunoprecipitation. Whole-cell patch clamp electrophysiology revealed that KCNE2 negative-shifts the voltage dependence and increases the rate of activation of the endothelial cell and cardiomyocyte-expressed Kv channel α subunit, Kv1.5 in CHO cells, whereas Testin did not alter Kv1.5 function. However, Testin nullified KCNE2 effects on Kv1.5 voltage dependence and gating kinetics. In contrast, Testin did not prevent KCNE2 regulation of KCNQ1 gating. The data identify a novel role for Testin as a tertiary ion channel regulatory protein. Future studies will address the potential role for KCNE2-Testin interactions in arterial and myocyte physiology and CAD.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"229-238"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38834361","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

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