Channels最新文献_第8页

Leptin-mediated ion channel regulation: PI3K pathways, physiological role, and therapeutic potential 瘦素介导的离子通道调节:PI3K通路、生理作用和治疗潜力

IF 3.3 3区生物学

Channels Pub Date : 2016-03-28 DOI: 10.1080/19336950.2016.1164373

Daniela Gavello, E. Carbone, V. Carabelli

{"title":"Leptin-mediated ion channel regulation: PI3K pathways, physiological role, and therapeutic potential","authors":"Daniela Gavello, E. Carbone, V. Carabelli","doi":"10.1080/19336950.2016.1164373","DOIUrl":"https://doi.org/10.1080/19336950.2016.1164373","url":null,"abstract":"ABSTRACT Leptin is produced by adipose tissue and identified as a “satiety signal,” informing the brain when the body has consumed enough food. Specific areas of the hypothalamus express leptin receptors (LEPRs) and are the primary site of leptin action for body weight regulation. In response to leptin, appetite is suppressed and energy expenditure allowed. Beside this hypothalamic action, leptin targets other brain areas in addition to neuroendocrine cells. LEPRs are expressed also in the hippocampus, neocortex, cerebellum, substantia nigra, pancreatic β-cells, and chromaffin cells of the adrenal gland. It is intriguing how leptin is able to activate different ionic conductances, thus affecting excitability, synaptic plasticity and neurotransmitter release, depending on the target cell. Most of the intracellular pathways activated by leptin and directed to ion channels involve PI3K, which in turn phosphorylates different downstream substrates, although parallel pathways involve AMPK and MAPK. In this review we will describe the effects of leptin on BK, KATP, KV, CaV, TRPC, NMDAR and AMPAR channels and clarify the landscape of pathways involved. Given the ability of leptin to influence neuronal excitability and synaptic plasticity by modulating ion channels activity, we also provide a short overview of the growing potentiality of leptin as therapeutic agent for treating neurological disorders.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2016-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83628510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 29

Why individual thermo sensation and pain perception varies? Clue of disruptive mutations in TRPVs from 2504 human genome data 为什么个体的热感觉和痛觉不同?2504个人类基因组数据中trpv破坏性突变的线索

IF 3.3 3区生物学

Channels Pub Date : 2016-03-10 DOI: 10.1080/19336950.2016.1162365

Arijit Ghosh, Navneet Kaur, Abhishek Kumar, C. Goswami

引用次数: 13

A painful tale about synthetic scorpion toxins 一个关于合成蝎子毒素的痛苦故事

IF 3.3 3区生物学

Channels Pub Date : 2016-03-10 DOI: 10.1080/19336950.2016.1163956

J. Salvatierra, F. Bosmans

引用次数: 0

Assessing the role of IKCa channels in generating the sAHP of CA1 hippocampal pyramidal cells 评估IKCa通道在CA1海马锥体细胞产生sAHP中的作用

IF 3.3 3区生物学

Channels Pub Date : 2016-03-07 DOI: 10.1080/19336950.2016.1161988

R. W. Turner, Hadhimulya Asmara, J. Engbers, J. Miclat, Arsalan P. Rizwan, Giriraj Sahu, G. Zamponi

引用次数: 21

TRPM3 gating in planar lipid bilayers defines peculiar agonist specificity 平面脂质双分子层中的TRPM3门控定义了特殊的激动剂特异性

IF 3.3 3区生物学

Channels Pub Date : 2016-02-22 DOI: 10.1080/19336950.2016.1155900

L. Demirkhanyan, K. Uchida, M. Tominaga, E. Zakharian

引用次数: 4

Surface dynamics of voltage-gated ion channels 电压门控离子通道的表面动力学

IF 3.3 3区生物学

Channels Pub Date : 2016-02-18 DOI: 10.1080/19336950.2016.1153210

M. Heine, A. Ciuraszkiewicz, A. Voigt, J. Heck, A. Bikbaev

引用次数: 14

Proteomic analysis of native cerebellar iFGF14 complexes 天然小脑iFGF14复合物的蛋白质组学分析

IF 3.3 3区生物学

Channels Pub Date : 2016-02-18 DOI: 10.1080/19336950.2016.1153203

Marie K. Bosch, J. Nerbonne, R. Reid Townsend, Haruko Miyazaki, N. Nukina, D. Ornitz, Céline Marionneau

{"title":"Proteomic analysis of native cerebellar iFGF14 complexes","authors":"Marie K. Bosch, J. Nerbonne, R. Reid Townsend, Haruko Miyazaki, N. Nukina, D. Ornitz, Céline Marionneau","doi":"10.1080/19336950.2016.1153203","DOIUrl":"https://doi.org/10.1080/19336950.2016.1153203","url":null,"abstract":"ABSTRACT Intracellular Fibroblast Growth Factor 14 (iFGF14) and the other intracellular FGFs (iFGF11-13) regulate the properties and densities of voltage-gated neuronal and cardiac Na+ (Nav) channels. Recent studies have demonstrated that the iFGFs can also regulate native voltage-gated Ca2+ (Cav) channels. In the present study, a mass spectrometry (MS)-based proteomic approach was used to identify the components of native cerebellar iFGF14 complexes. Using an anti-iFGF14 antibody, native iFGF14 complexes were immunoprecipitated from wild type adult mouse cerebellum. Parallel control experiments were performed on cerebellar proteins isolated from mice (Fgf14−/−) harboring a targeted disruption of the Fgf14 locus. MS analyses of immunoprecipitated proteins demonstrated that the vast majority of proteins identified in native cerebellar iFGF14 complexes are Nav channel pore-forming (α) subunits or proteins previously reported to interact with Nav α subunits. In contrast, no Cav channel α or accessory subunits were revealed in cerebellar iFGF14 immunoprecipitates. Additional experiments were completed using an anti-PanNav antibody to immunoprecipitate Nav channel complexes from wild type and Fgf14−/− mouse cerebellum. Western blot and MS analyses revealed that the loss of iFGF14 does not measurably affect the protein composition or the relative abundance of Nav channel interacting proteins in native adult mouse cerebellar Nav channel complexes.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2016-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83068039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Governing effect of regulatory proteins for Cl−/HCO3− exchanger 2 activity 调节蛋白对Cl−/HCO3−交换器2活性的调控作用

IF 3.3 3区生物学

Channels Pub Date : 2016-02-08 DOI: 10.1080/19336950.2015.1134068

Y. Jeong, J. Hong

{"title":"Governing effect of regulatory proteins for Cl−/HCO3− exchanger 2 activity","authors":"Y. Jeong, J. Hong","doi":"10.1080/19336950.2015.1134068","DOIUrl":"https://doi.org/10.1080/19336950.2015.1134068","url":null,"abstract":"ABSTRACT Anion exchanger 2 (AE2) has a critical role in epithelial cells and is involved in the ionic homeostasis such as Cl− uptake and HCO3− secretion. However, little is known about the regulatory mechanism of AE2. The main goal of the present study was to investigate potential regulators, such as spinophilin (SPL), inositol-1,4,5-trisphosphate [IP3] receptors binding protein released with IP3 (IRBIT), STE20/SPS1-related proline/alanine-rich kinase (SPAK) kinase, and carbonic anhydrase XII (CA XII). We found that SPL binds to AE2 and markedly increased the Cl−/HCO3− exchange activity of AE2. Especially SPL 1–480 domain is required for enhancing AE2 activity. For other regulatory components that affect the fidelity of fluid and HCO3− secretion, IRBIT and SPAK had no effect on the activity of AE2 and no protein-protein interaction with AE2. It has been proposed that CA activity is closely associated with AE activity. In this study, we provide evidence that the basolateral membrane-associated CA isoform CA XII significantly increased the activity of AE2 and co-localized with AE2 to the plasma membrane. Collectively, SPL and CA XII enhanced the Cl−/HCO3− exchange activity of AE2. The modulating action of these regulatory proteins could serve as potential therapeutic targets for secretory diseases mediated by AE2.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2016-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79446993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Mutant bacterial sodium channels as models for local anesthetic block of eukaryotic proteins 突变细菌钠通道作为真核蛋白局部麻醉阻滞的模型

IF 3.3 3区生物学

Channels Pub Date : 2016-02-06 DOI: 10.1080/19336950.2016.1148224

Natalie E. Smith, B. Corry

{"title":"Mutant bacterial sodium channels as models for local anesthetic block of eukaryotic proteins","authors":"Natalie E. Smith, B. Corry","doi":"10.1080/19336950.2016.1148224","DOIUrl":"https://doi.org/10.1080/19336950.2016.1148224","url":null,"abstract":"ABSTRACT Voltage gated sodium channels are the target of a range of local anesthetic, anti-epileptic and anti-arrhythmic compounds. But, gaining a molecular level understanding of their mode of action is difficult as we only have atomic resolution structures of bacterial sodium channels not their eukaryotic counterparts. In this study we used molecular dynamics simulations to demonstrate that the binding sites of both the local anesthetic benzocaine and the anti-epileptic phenytoin to the bacterial sodium channel NavAb can be altered significantly by the introduction of point mutations. Free energy techniques were applied to show that increased aromaticity in the pore of the channel, used to emulate the aromatic residues observed in eukaryotic Nav1.2, led to changes in the location of binding and dissociation constants of each drug relative to wild type NavAb. Further, binding locations and dissociation constants obtained for both benzocaine (660 μM) and phenytoin (1 μ M) in the mutant channels were within the range expected from experimental values obtained from drug binding to eukaryotic sodium channels, indicating that these mutant NavAb may be a better model for drug binding to eukaryotic channels than the wild type.","PeriodicalId":9750,"journal":{"name":"Channels","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2016-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83248049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Single calcium channels stand out in the crowd 单一钙通道在人群中脱颖而出

IF 3.3 3区生物学

Channels Pub Date : 2016-01-26 DOI: 10.1080/19336950.2015.1119633

M. Dittrich, S. D. Meriney

引用次数: 1