Channels (Austin, Tex.)最新文献_第7页

Conductance stability and Na+ interaction with Shab K+ channels under low K+ conditions. 在低K+条件下，电导稳定性和Na+与Shab K+通道的相互作用。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1993037

Froylán Gómez-Lagunas, Elisa Carrillo, Carolina Barriga-Montoya

{"title":"Conductance stability and Na+ interaction with Shab K+ channels under low K+ conditions.","authors":"Froylán Gómez-Lagunas, Elisa Carrillo, Carolina Barriga-Montoya","doi":"10.1080/19336950.2021.1993037","DOIUrl":"10.1080/19336950.2021.1993037","url":null,"abstract":"K+ ions exert a structural effect that brings stability to K+ selective pores. Thus, upon bathing Shab channels in 0 K+ solutions the ion conductance, GK, irreversibly collapses. Related to this, studies with isolated KcsA channels have suggested that there is a transition [K+] around which the pore takes one of two conformations, either the low (non-conducting) or high K+ (conducting) crystal structures. We examined this premise by looking at the K+-dependency of GK stability of Shab channels within the cell membrane environment. We found that: K+ effect on GK stability is highly asymmetrical, and that as internal K+ is replaced by Na+ GK drops in a way that suggests a transition internal [K+]. Additionally, we found that external permeant ions inhibit GK drop with a potency that differs from the global selectivity-sequence of K+ pores; the non-permeant TEA inhibited GK drop in a K+-dependent manner. Upon lowering internal [K+] we observed an influx of Na+ at negative potentials. Na+ influx was halted by physiological external [K+], which also restored GK stability. Hyperpolarized potentials afforded GK stability but, as expected, do not restore GK selectivity. For completeness, Na+ interaction with Shab was also assessed at depolarized potentials by looking at Na block followed by permeation (pore unblock) at positive potentials, in solutions approaching the 0 K+ limit. The stabilizing effect of negative potentials along with the non-parallel variation of Na+ permeability and conductance-stability herein reported, show that pore stability and selectivity, although related, are not strictly coupled.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"648-665"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39524841","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

Alpha lipoic acid attenuates evoked and spontaneous pain following surgical skin incision in rats. α-硫辛酸可减轻大鼠皮肤手术切口后的诱发痛和自发痛。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1907058

Sonja Lj Joksimovic, Nathan Lamborn, Vesna Jevtovic-Todorovic, Slobodan M Todorovic

引用次数: 0

TRPM2 in ischemic stroke: Structure, molecular mechanisms, and drug intervention. 缺血性中风中的 TRPM2：结构、分子机制和药物干预。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1870088

Qing Wang, Ning Liu, Yuan-Shu Ni, Jia-Mei Yang, Lin Ma, Xiao-Bing Lan, Jing Wu, Jian-Guo Niu, Jian-Qiang Yu

{"title":"TRPM2 in ischemic stroke: Structure, molecular mechanisms, and drug intervention.","authors":"Qing Wang, Ning Liu, Yuan-Shu Ni, Jia-Mei Yang, Lin Ma, Xiao-Bing Lan, Jing Wu, Jian-Guo Niu, Jian-Qiang Yu","doi":"10.1080/19336950.2020.1870088","DOIUrl":"10.1080/19336950.2020.1870088","url":null,"abstract":"Ischemic stroke has a high lethality rate worldwide, and novel treatments are limited. Calcium overload is considered to be one of the mechanisms of cerebral ischemia. Transient receptor potential melastatin 2 (TRPM2) is a reactive oxygen species (ROS)-sensitive calcium channel. Cerebral ischemia-induced TRPM2 activation triggers abnormal intracellular Ca2+ accumulation and cell death, which in turn causes irreversible brain damage. Thus, TRPM2 has emerged as a new therapeutic target for ischemic stroke. This review provides data on the expression, structure, and function of TRPM2 and illustrates its cellular and molecular mechanisms in ischemic stroke. Natural and synthetic TRPM2 inhibitors (both specific and nonspecific) are also summarized. The three-dimensional protein structure of TRPM2 has been identified, and we speculate that molecular simulation techniques will be essential for developing new drugs that block TRPM2 channels. These insights about TRPM2 may be the key to find potent therapeutic approaches for the treatment of ischemic stroke.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"136-154"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38827012","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

Pan-cancer analysis and single-cell analysis revealed the role of ABCC5 transporter in hepatocellular carcinoma. 泛癌分析和单细胞分析揭示了ABCC5转运体在肝细胞癌中的作用。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1968592

Liang Chen, Zhonghua Yang, Yuan Cao, Yiming Hu, Wei Bao, Dan Wu, Li Hu, Jiaheng Xie, Hongzhu Yu

{"title":"Pan-cancer analysis and single-cell analysis revealed the role of ABCC5 transporter in hepatocellular carcinoma.","authors":"Liang Chen, Zhonghua Yang, Yuan Cao, Yiming Hu, Wei Bao, Dan Wu, Li Hu, Jiaheng Xie, Hongzhu Yu","doi":"10.1080/19336950.2021.1968592","DOIUrl":"https://doi.org/10.1080/19336950.2021.1968592","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. Many patients with hepatocellular carcinoma are diagnosed at an advanced stage because the early symptoms are not obvious. For advanced hepatocellular carcinoma, immunotherapy and targeted therapy seem to be a promising direction. Finding a new prognostic marker for hepatocellular carcinoma and exploring its role in the immune microenvironment is of great value. ABCC transporters have previously been associated with drug resistance in hepatocellular tumors, but the exact mechanism remains unclear. Here, we conducted a study on ABCC5 in HCC and found that the expression of ABCC5 was up-regulated in HCC and was associated with poor prognosis. Further exploration revealed that ABCC5 was associated with immune infiltration of hepatocellular carcinoma. Single-cell analysis revealed a potential relationship between ABCC5 and immune cell differentiation. Therefore, it is significant to continue to explore the role of ABCC5 in hepatocellular carcinoma.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"541-554"},"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/fc/e4/KCHL_15_1968592.PMC8437464.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39411898","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: 7

Structure and Function of the Bestrophin family of calcium-activated chloride channels. 钙活化氯离子通道Bestrophin家族的结构和功能。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1981625

Aaron P Owji, Alec Kittredge, Yu Zhang, Tingting Yang

{"title":"Structure and Function of the Bestrophin family of calcium-activated chloride channels.","authors":"Aaron P Owji, Alec Kittredge, Yu Zhang, Tingting Yang","doi":"10.1080/19336950.2021.1981625","DOIUrl":"https://doi.org/10.1080/19336950.2021.1981625","url":null,"abstract":"Bestrophins are a family of calcium-activated chloride channels (CaCCs) with relevance to human physiology and a myriad of eye diseases termed \"bestrophinopathies\". Since the identification of bestrophins as CaCCs nearly two decades ago, extensive studies from electrophysiological and structural biology perspectives have sought to define their key channel features including calcium sensing, gating, inactivation, and anion selectivity. The initial X-ray crystallography studies on the prokaryotic homolog of Best1, Klebsiella pneumoniae (KpBest), and the Best1 homolog from Gallus gallus (chicken Best1, cBest1), laid the foundational groundwork for establishing the architecture of Best1. Recent progress utilizing single-particle cryogenic electron microscopy has further elucidated the molecular mechanism of gating in cBest1 and, separately, the structure of Best2 from Bos taurus (bovine Best2, bBest2). Meanwhile, whole-cell patch clamp, planar lipid bilayer, and other electrophysiologic analyses using these models as well as the human Best1 (hBest1) have provided ample evidence describing the functional properties of the bestrophin channels. This review seeks to consolidate these structural and functional results to paint a broad picture of the underlying mechanisms comprising the bestrophin family's structure-function relationship.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"604-623"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39491582","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: 7

The anchor domain is critical for Piezo1 channel mechanosensitivity. 锚域对于Piezo1通道的机械敏感性至关重要。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1923199

Jinyuan Vero Li, Charles D Cox, Boris Martinac

{"title":"The anchor domain is critical for Piezo1 channel mechanosensitivity.","authors":"Jinyuan Vero Li, Charles D Cox, Boris Martinac","doi":"10.1080/19336950.2021.1923199","DOIUrl":"10.1080/19336950.2021.1923199","url":null,"abstract":"The mechanosensitive channel Piezo1 is a crucial membrane mechanosensor ubiquitously expressed in mammalian cell types. Critical to its function in mechanosensory transduction is its ability to change conformation in response to applied mechanical force. Here, we interrogate the role of the anchor domain in the mechanically induced gating of human Piezo1 channels. Using the insertion of glycine residues at each corner of the triangular-shaped anchor domain to decouple this domain we provide evidence that the anchor is important in Piezo1 mechano-gating. Insertion of two extra glycine residues between the anchor and the outer helix of human Piezo1 causes abrogated inactivation and reduced mechanosensitivity. Whereas inserting two glycine residues at the apex of the anchor domain at the conserved amino acid P2113 causes the channel to be more sensitive to membrane forces. Correlation of stretch sensitivity with the volume of the neighboring amino acid, natively a phenylalanine (F2114), suggests this is caused by removal of steric hindrance on the inner pore-lining helix. Smaller volume amino acids at this residue increase sensitivity whereas larger volume reduces mechanosensitivity. The combined data show that the anchor domain is a critical region for Piezo1-mediated force transduction.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"438-446"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38889499","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

Efficient expression of a cnidarian peptide-gated ion channel in mammalian cells. 在哺乳动物细胞中高效表达网状肽门控离子通道。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1882762

Michèle Bachmann, Audrey Ortega-Ramírez, Lilia Leisle, Stefan Gründer

引用次数: 0

Late sodium current and calcium homeostasis in arrhythmogenesis. 心律失常发生过程中的晚期钠电流和钙稳态

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1854986

Kornél Kistamás, Tamás Hézső, Balázs Horváth, Péter P Nánási

引用次数: 0

Immunomagnetic separation is a suitable method for electrophysiology and ion channel pharmacology studies on T cells. 免疫磁性分离是对 T 细胞进行电生理学和离子通道药理学研究的一种合适方法。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1859753

Gabor Tajti, Tibor Gabor Szanto, Agota Csoti, Greta Racz, César Evaristo, Peter Hajdu, Gyorgy Panyi

{"title":"Immunomagnetic separation is a suitable method for electrophysiology and ion channel pharmacology studies on T cells.","authors":"Gabor Tajti, Tibor Gabor Szanto, Agota Csoti, Greta Racz, César Evaristo, Peter Hajdu, Gyorgy Panyi","doi":"10.1080/19336950.2020.1859753","DOIUrl":"10.1080/19336950.2020.1859753","url":null,"abstract":"Ion channels play pivotal role in the physiological and pathological function of immune cells. As immune cells represent a functionally diverse population, subtype-specific functional studies, such as single-cell electrophysiology require proper subset identification and separation. Magnetic-activated cell sorting (MACS) techniques provide an alternative to fluorescence-activated cell sorting (FACS), however, the potential impact of MACS-related beads on the biophysical and pharmacological properties of the ion channels were not studied yet. We studied the aforementioned properties of the voltage-gated Kv1.3 K+ channel in activated CD4+ T-cells as well as the membrane capacitance using whole-cell patch-clamp following immunomagnetic positive separation, using the REAlease® kit. This kit allows three experimental configurations: bead-bound configuration, bead-free configuration following the removal of magnetic beads, and the label-free configuration following removal of CD4 recognizing antibody fragments. As controls, we used FACS separation as well as immunomagnetic negative selection. The membrane capacitance and of the biophysical parameters of Kv1.3 gating, voltage-dependence of steady-state activation and inactivation kinetics of the current were not affected by the presence of MACS-related compounds on the cell surface. We found subtle differences in the activation kinetics of the Kv1.3 current that could not be explained by the presence of MACS-related compounds. Neither the equilibrium block of Kv1.3 by TEA+ or charybdotoxin (ChTx) nor the kinetics of ChTx block are affected by the presence of the magnetics beads on the cell surface. Based on our results MACS is a suitable method to separate cells for studying ion channels in non-excitable cells, such as T-lymphocytes.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"53-66"},"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/02/ff/KCHL_15_1859753.PMC7781520.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38745409","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

Assessing the impact of pain-linked Nav1.7 variants: An example of two variants with no biophysical effect. 评估与疼痛相关的 Nav1.7 变异的影响：以两个无生物物理效应的变体为例。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1870087

Kim Le Cann, Jannis E Meents, Vishal Sudha Bhagavath Eswaran, Maike F Dohrn, Raya Bott, Andrea Maier, Martin Bialer, Petra Hautvast, Andelain Erickson, Roman Rolke, Markus Rothermel, Jannis Körner, Ingo Kurth, Angelika Lampert

{"title":"Assessing the impact of pain-linked Nav1.7 variants: An example of two variants with no biophysical effect.","authors":"Kim Le Cann, Jannis E Meents, Vishal Sudha Bhagavath Eswaran, Maike F Dohrn, Raya Bott, Andrea Maier, Martin Bialer, Petra Hautvast, Andelain Erickson, Roman Rolke, Markus Rothermel, Jannis Körner, Ingo Kurth, Angelika Lampert","doi":"10.1080/19336950.2020.1870087","DOIUrl":"10.1080/19336950.2020.1870087","url":null,"abstract":"Mutations in the voltage-gated sodium channel Nav1.7 are linked to human pain. The Nav1.7/N1245S variant was described before in several patients suffering from primary erythromelalgia and/or olfactory hypersensitivity. We have identified this variant in a pain patient and a patient suffering from severe and life-threatening orthostatic hypotension. In addition, we report a female patient suffering from muscle pain and carrying the Nav1.7/E1139K variant. We tested both Nav1.7 variants by whole-cell voltage-clamp recordings in HEK293 cells, revealing a slightly enhanced current density for the N1245S variant when co-expressed with the β1 subunit. This effect was counteracted by an enhanced slow inactivation. Both variants showed similar voltage dependence of activation and steady-state fast inactivation, as well as kinetics of fast inactivation, deactivation, and use-dependency compared to WT Nav1.7. Finally, homology modeling revealed that the N1245S substitution results in different intramolecular interaction partners. Taken together, these experiments do not point to a clear pathogenic effect of either the N1245S or E1139K variant and suggest they may not be solely responsible for the patients' pain symptoms. As discussed previously for other variants, investigations in heterologous expression systems may not sufficiently mimic the pathophysiological situation in pain patients, and single nucleotide variants in other genes or modulatory proteins are necessary for these specific variants to show their effect. Our findings stress that biophysical investigations of ion channel mutations need to be evaluated with care and should preferably be supplemented with studies investigating the mutations in their context, ideally in human sensory neurons.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"208-228"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38852837","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