Channels (Austin, Tex.)最新文献_第7页

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

Regulatory mechanisms of mitochondrial BK_Ca channels. 线粒体 BKCa 通道的调节机制。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1919463

Ana L González-Cota, Carmen Santana-Calvo, Rocío Servín-Vences, Gerardo Orta, Enrique Balderas

{"title":"Regulatory mechanisms of mitochondrial BKCa channels.","authors":"Ana L González-Cota, Carmen Santana-Calvo, Rocío Servín-Vences, Gerardo Orta, Enrique Balderas","doi":"10.1080/19336950.2021.1919463","DOIUrl":"10.1080/19336950.2021.1919463","url":null,"abstract":"The mitochondrial BKCa channel (mitoBKCa) is a splice variant of plasma membrane BKCa (Maxi-K, BKCa, Slo1, KCa1.1). While a high-resolution structure of mitoBKCa is not available yet, functional and structural studies of the plasma membrane BKCa have provided important clues on the gating of the channel by voltage and Ca2+, as well as the interaction with auxiliary subunits. To date, we know that the control of expression of mitoBKCa, targeting and voltage-sensitivity strongly depends on its association with its regulatory β1-subunit, which overall participate in the control of mitochondrial Ca2+-overload in cardiac myocytes. Moreover, novel regulatory mechanisms of mitoBKCa such as β-subunits and amyloid-β have recently been proposed. However, major basic questions including how the regulatory BKCa-β1-subunit reaches mitochondria and the mechanism through which amyloid-β impairs mitoBKCa channel function remain to be addressed.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"424-437"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38954825","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

Changes in peripheral HCN2 channels during persistent inflammation. 持续炎症期间外周 HCN2 通道的变化

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2020.1870086

L-A R Jansen, L A Forster, X L Smith, M Rubaharan, A Z Murphy, D J Baro

{"title":"Changes in peripheral HCN2 channels during persistent inflammation.","authors":"L-A R Jansen, L A Forster, X L Smith, M Rubaharan, A Z Murphy, D J Baro","doi":"10.1080/19336950.2020.1870086","DOIUrl":"10.1080/19336950.2020.1870086","url":null,"abstract":"Nociceptor sensitization following nerve injury or inflammation leads to chronic pain. An increase in the nociceptor hyperpolarization-activated current, Ih, is observed in many models of pathological pain. Pharmacological blockade of Ih prevents the mechanical and thermal hypersensitivity that occurs during pathological pain. Alterations in the Hyperpolarization-activated Cyclic Nucleotide-gated ion channel 2 (HCN2) mediate Ih-dependent thermal and mechanical hyperalgesia. Limited knowledge exists regarding the nature of these changes during chronic inflammatory pain. Modifications in HCN2 expression and post-translational SUMOylation have been observed in the Complete Freund's Adjuvant (CFA) model of chronic inflammatory pain. Intra-plantar injection of CFA into the rat hindpaw induces unilateral hyperalgesia that is sustained for up to 14 days following injection. The hindpaw is innervated by primary afferents in lumbar DRG, L4-6. Adjustments in HCN2 expression and SUMOylation have been well-documented for L5 DRG during the first 7 days of CFA-induced inflammation. Here, we examine bilateral L4 and L6 DRG at day 1 and day 3 post-CFA. Using L4 and L6 DRG cryosections, HCN2 expression and SUMOylation were measured with immunohistochemistry and proximity ligation assays, respectively. Our findings indicate that intra-plantar injection of CFA elicited a bilateral increase in HCN2 expression in L4 and L6 DRG at day 1, but not day 3, and enhanced HCN2 SUMOylation in ipsilateral L6 DRG at day 1 and day 3. Changes in HCN2 expression and SUMOylation were transient over this time course. Our study suggests that HCN2 is regulated by multiple mechanisms during CFA-induced inflammation.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"165-179"},"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/e0/c6/KCHL_15_1870086.PMC7808421.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38801496","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

Bibliometric analysis of nicotinic acetylcholine receptors channel research (2000-2020). 烟碱乙酰胆碱受体通道研究的文献计量学分析(2000-2020)。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1882113

Xueping Zhu, Yan Zhou, Guozhen Yuan, Jingjing Shi, Shuai Shi, Limei Zhang, Ruoning Chai, Yihang Du, Chenglin Duan, Yuanhui Hu

{"title":"Bibliometric analysis of nicotinic acetylcholine receptors channel research (2000-2020).","authors":"Xueping Zhu, Yan Zhou, Guozhen Yuan, Jingjing Shi, Shuai Shi, Limei Zhang, Ruoning Chai, Yihang Du, Chenglin Duan, Yuanhui Hu","doi":"10.1080/19336950.2021.1882113","DOIUrl":"10.1080/19336950.2021.1882113","url":null,"abstract":"To explore the research status, hotspots, and trends in research on nicotinic acetylcholine receptor (nAChR) channel. The Web of Science core collection database from 2000 to 2020 was used as the data source. The visual analysis software VOSviewer1.6.16 and Citespace5.7 R3 were used to visualize the studies of the nAChR channel. The national/institutional distribution, journal distribution, authors, and related research were discussed. A total of 5,794 articles were obtained. The USA and the Utah System of Higher Education were the most productive country and institution for nAChR channel research. Journal of Biological Chemistry was the most productive journal (212) and the most productive researcher was McIntosh, J. Michael. The first highly co-cited article was \"Refined structure of the nicotinic acetylcholine receptor at 4A resolution.\" The most researched area was neurosciences neurology. The hot spots of nAChR channel research were \"subunit and structure of nAChR,\" \"activation/agonist of nAChR channel,\" and \"Changes in nAChRs With Alzheimer's Disease.\" The top three research frontiers of nAChR channel research were \"neuropathic pain,\" \"neuroinflammation,\" and \"α7 nACHR.\" The study provides a perspective to visualize and analyze hotspots and emerging trends in the nAChR channel.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"298-309"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25392010","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

Molecular mechanisms of activation and regulation of ANO1-Encoded Ca²⁺-Activated Cl^- channels. ano1编码的Ca2+激活Cl-通道的激活和调控的分子机制。

Channels (Austin, Tex.) Pub Date : 2021-12-01 DOI: 10.1080/19336950.2021.1975411

M B Hawn, E Akin, H C Hartzell, I A Greenwood, N Leblanc

{"title":"Molecular mechanisms of activation and regulation of ANO1-Encoded Ca2+-Activated Cl- channels.","authors":"M B Hawn, E Akin, H C Hartzell, I A Greenwood, N Leblanc","doi":"10.1080/19336950.2021.1975411","DOIUrl":"10.1080/19336950.2021.1975411","url":null,"abstract":"Ca2+-activated Cl- channels (CaCCs) perform a multitude of functions including the control of cell excitability, regulation of cell volume and ionic homeostasis, exocrine and endocrine secretion, fertilization, amplification of olfactory sensory function, and control of smooth muscle cell contractility. CaCCs are the translated products of two members (ANO1 and ANO2, also known as TMEM16A and TMEM16B) of the Anoctamin family of genes comprising ten paralogs. This review focuses on recent progress in understanding the molecular mechanisms involved in the regulation of ANO1 by cytoplasmic Ca2+, post-translational modifications, and how the channel protein interacts with membrane lipids and protein partners. After first reviewing the basic properties of native CaCCs, we then present a brief historical perspective highlighting controversies about their molecular identity in native cells. This is followed by a summary of the fundamental biophysical and structural properties of ANO1. We specifically address whether the channel is directly activated by internal Ca2+ or indirectly through the intervention of the Ca2+-binding protein Calmodulin (CaM), and the structural domains responsible for Ca2+- and voltage-dependent gating. We then review the regulation of ANO1 by internal ATP, Calmodulin-dependent protein kinase II-(CaMKII)-mediated phosphorylation and phosphatase activity, membrane lipids such as the phospholipid phosphatidyl-(4,5)-bisphosphate (PIP2), free fatty acids and cholesterol, and the cytoskeleton. The article ends with a survey of physical and functional interactions of ANO1 with other membrane proteins such as CLCA1/2, inositol trisphosphate and ryanodine receptors in the endoplasmic reticulum, several members of the TRP channel family, and the ancillary Κ+ channel β subunits KCNE1/5.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":" ","pages":"569-603"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39390343","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: 15