Pub Date : 2016-03-10DOI: 10.1080/19336950.2016.1163956
J. Salvatierra, F. Bosmans
Within the voltage-gated NaC (Nav) channel gene family, the Nav1.7 isoform (SCN9A) has been receiving a great deal of scientific and clinical attention after investigators uncovered its strategic role in various pain syndromes. As a result, Nav1.7 became somewhat of a Holy Grail for researchers in academia as well as the pharmaceutical industry who are interested in discovering novel, target-specific non-narcotic pain therapeutics. However, clinically-used Nav channel drugs are prone to dose-limiting side effects because they typically target the conserved pore region and therefore do not discriminate between isoforms. In contrast, Nav channel voltage-sensing domains (VSDs) differ substantially between isoforms and regulate pore opening and closing (i.e. gating). As such, it should be possible to design effective drugs that target the gating process of a particular Nav channel isoform without physically blocking the pore, a fascinating concept that has recently led to the discovery of Nav1.7-specific small-molecule compounds. 4,5
{"title":"A painful tale about synthetic scorpion toxins","authors":"J. Salvatierra, F. Bosmans","doi":"10.1080/19336950.2016.1163956","DOIUrl":"https://doi.org/10.1080/19336950.2016.1163956","url":null,"abstract":"Within the voltage-gated NaC (Nav) channel gene family, the Nav1.7 isoform (SCN9A) has been receiving a great deal of scientific and clinical attention after investigators uncovered its strategic role in various pain syndromes. As a result, Nav1.7 became somewhat of a Holy Grail for researchers in academia as well as the pharmaceutical industry who are interested in discovering novel, target-specific non-narcotic pain therapeutics. However, clinically-used Nav channel drugs are prone to dose-limiting side effects because they typically target the conserved pore region and therefore do not discriminate between isoforms. In contrast, Nav channel voltage-sensing domains (VSDs) differ substantially between isoforms and regulate pore opening and closing (i.e. gating). As such, it should be possible to design effective drugs that target the gating process of a particular Nav channel isoform without physically blocking the pore, a fascinating concept that has recently led to the discovery of Nav1.7-specific small-molecule compounds. 4,5","PeriodicalId":9750,"journal":{"name":"Channels","volume":"42 1","pages":"147 - 256 - 257"},"PeriodicalIF":3.3,"publicationDate":"2016-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78783106","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}
Pub Date : 2016-03-07DOI: 10.1080/19336950.2016.1161988
R. W. Turner, Hadhimulya Asmara, J. Engbers, J. Miclat, Arsalan P. Rizwan, Giriraj Sahu, G. Zamponi
ABSTRACT Our previous work reported that KCa3.1 (IKCa) channels are expressed in CA1 hippocampal pyramidal cells and contribute to the slow afterhyperpolarization that regulates spike accommodation in these cells. The current report presents data from single cell RT-PCR that further reveals mRNA in CA1 cells that corresponds to the sequence of an IKCa channel from transmembrane segments 5 through 6 including the pore region, revealing the established binding sites for 4 different IKCa channel blockers. A comparison of methods to internally apply the IKCa channel blocker TRAM-34 shows that including the drug in an electrode from the onset of an experiment is unviable given the speed of drug action upon gaining access for whole-cell recordings. Together the data firmly establish IKCa channel expression in CA1 neurons and clarify methodological requirements to obtain a block of IKCa channel activity through internal application of TRAM-34.
{"title":"Assessing the role of IKCa channels in generating the sAHP of CA1 hippocampal pyramidal cells","authors":"R. W. Turner, Hadhimulya Asmara, J. Engbers, J. Miclat, Arsalan P. Rizwan, Giriraj Sahu, G. Zamponi","doi":"10.1080/19336950.2016.1161988","DOIUrl":"https://doi.org/10.1080/19336950.2016.1161988","url":null,"abstract":"ABSTRACT Our previous work reported that KCa3.1 (IKCa) channels are expressed in CA1 hippocampal pyramidal cells and contribute to the slow afterhyperpolarization that regulates spike accommodation in these cells. The current report presents data from single cell RT-PCR that further reveals mRNA in CA1 cells that corresponds to the sequence of an IKCa channel from transmembrane segments 5 through 6 including the pore region, revealing the established binding sites for 4 different IKCa channel blockers. A comparison of methods to internally apply the IKCa channel blocker TRAM-34 shows that including the drug in an electrode from the onset of an experiment is unviable given the speed of drug action upon gaining access for whole-cell recordings. Together the data firmly establish IKCa channel expression in CA1 neurons and clarify methodological requirements to obtain a block of IKCa channel activity through internal application of TRAM-34.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"379 1","pages":"313 - 319"},"PeriodicalIF":3.3,"publicationDate":"2016-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75153335","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}
Pub Date : 2016-02-22DOI: 10.1080/19336950.2016.1155900
L. Demirkhanyan, K. Uchida, M. Tominaga, E. Zakharian
Lusine Demirkhanyan, Kunitoshi Uchida, Makoto Tominaga, and Eleonora Zakharian Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL, USA; Division of Cell Signaling, National Institute of Physiological Sciences (Okazaki Institute of Integrative Bioscience), Okazaki, Aichi, Japan; Department of Physiological Sciences, The Graduate University of Advanced Studies, Shonan Village, Hayama, Kanagawa, Japan
{"title":"TRPM3 gating in planar lipid bilayers defines peculiar agonist specificity","authors":"L. Demirkhanyan, K. Uchida, M. Tominaga, E. Zakharian","doi":"10.1080/19336950.2016.1155900","DOIUrl":"https://doi.org/10.1080/19336950.2016.1155900","url":null,"abstract":"Lusine Demirkhanyan, Kunitoshi Uchida, Makoto Tominaga, and Eleonora Zakharian Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL, USA; Division of Cell Signaling, National Institute of Physiological Sciences (Okazaki Institute of Integrative Bioscience), Okazaki, Aichi, Japan; Department of Physiological Sciences, The Graduate University of Advanced Studies, Shonan Village, Hayama, Kanagawa, Japan","PeriodicalId":9750,"journal":{"name":"Channels","volume":"75 1","pages":"258 - 260"},"PeriodicalIF":3.3,"publicationDate":"2016-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86999793","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}
Pub Date : 2016-02-18DOI: 10.1080/19336950.2016.1153210
M. Heine, A. Ciuraszkiewicz, A. Voigt, J. Heck, A. Bikbaev
ABSTRACT Neurons encode information in fast changes of the membrane potential, and thus electrical membrane properties are critically important for the integration and processing of synaptic inputs by a neuron. These electrical properties are largely determined by ion channels embedded in the membrane. The distribution of most ion channels in the membrane is not spatially uniform: they undergo activity-driven changes in the range of minutes to days. Even in the range of milliseconds, the composition and topology of ion channels are not static but engage in highly dynamic processes including stochastic or activity-dependent transient association of the pore-forming and auxiliary subunits, lateral diffusion, as well as clustering of different channels. In this review we briefly discuss the potential impact of mobile sodium, calcium and potassium ion channels and the functional significance of this for individual neurons and neuronal networks.
{"title":"Surface dynamics of voltage-gated ion channels","authors":"M. Heine, A. Ciuraszkiewicz, A. Voigt, J. Heck, A. Bikbaev","doi":"10.1080/19336950.2016.1153210","DOIUrl":"https://doi.org/10.1080/19336950.2016.1153210","url":null,"abstract":"ABSTRACT Neurons encode information in fast changes of the membrane potential, and thus electrical membrane properties are critically important for the integration and processing of synaptic inputs by a neuron. These electrical properties are largely determined by ion channels embedded in the membrane. The distribution of most ion channels in the membrane is not spatially uniform: they undergo activity-driven changes in the range of minutes to days. Even in the range of milliseconds, the composition and topology of ion channels are not static but engage in highly dynamic processes including stochastic or activity-dependent transient association of the pore-forming and auxiliary subunits, lateral diffusion, as well as clustering of different channels. In this review we briefly discuss the potential impact of mobile sodium, calcium and potassium ion channels and the functional significance of this for individual neurons and neuronal networks.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"83 1","pages":"267 - 281"},"PeriodicalIF":3.3,"publicationDate":"2016-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82862396","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}
Pub Date : 2016-02-18DOI: 10.1080/19336950.2016.1153203
Marie K. Bosch, J. Nerbonne, R. Reid Townsend, Haruko Miyazaki, N. Nukina, D. Ornitz, Céline Marionneau
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.
{"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":"19 1","pages":"297 - 312"},"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}
Pub Date : 2016-02-08DOI: 10.1080/19336950.2015.1134068
Y. Jeong, J. Hong
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.
{"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":"94 1","pages":"214 - 224"},"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}
Pub Date : 2016-02-06DOI: 10.1080/19336950.2016.1148224
Natalie E. Smith, B. Corry
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.
{"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":"14 1","pages":"225 - 237"},"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}
Pub Date : 2016-01-26DOI: 10.1080/19336950.2015.1119633
M. Dittrich, S. D. Meriney
A key property of many synapses in the nervous system is their ability to trigger fast fusion of transmitter-containing vesicles at specialized release sites (active zones; AZs). This raises the qu...
神经系统中许多突触的一个关键特性是它们能够在特定的释放位点(活跃区;az)。这就提出了…
{"title":"Single calcium channels stand out in the crowd","authors":"M. Dittrich, S. D. Meriney","doi":"10.1080/19336950.2015.1119633","DOIUrl":"https://doi.org/10.1080/19336950.2015.1119633","url":null,"abstract":"A key property of many synapses in the nervous system is their ability to trigger fast fusion of transmitter-containing vesicles at specialized release sites (active zones; AZs). This raises the qu...","PeriodicalId":9750,"journal":{"name":"Channels","volume":"452 1","pages":"71 - 72"},"PeriodicalIF":3.3,"publicationDate":"2016-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82926871","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}
Pub Date : 2016-01-26DOI: 10.1080/19336950.2015.1126010
A. Billet, Yanlin Jia, T. Jensen, Yue‐xian Hou, X. Chang, J. Riordan, J. Hanrahan
ABSTRACT The CFTR chloride channel is tightly regulated by phosphorylation at multiple serine residues. Recently it has been proposed that its activity is also regulated by tyrosine kinases, however the tyrosine phosphorylation sites remain to be identified. In this study we examined 2 candidate tyrosine residues near the boundary between the first nucleotide binding domain and the R domain, a region which is important for channel function but devoid of PKA consensus sequences. Mutating tyrosines at positions 625 and 627 dramatically reduced responses to Src or Pyk2 without altering the activation by PKA, suggesting they may contribute to CFTR regulation.
{"title":"Potential sites of CFTR activation by tyrosine kinases","authors":"A. Billet, Yanlin Jia, T. Jensen, Yue‐xian Hou, X. Chang, J. Riordan, J. Hanrahan","doi":"10.1080/19336950.2015.1126010","DOIUrl":"https://doi.org/10.1080/19336950.2015.1126010","url":null,"abstract":"ABSTRACT The CFTR chloride channel is tightly regulated by phosphorylation at multiple serine residues. Recently it has been proposed that its activity is also regulated by tyrosine kinases, however the tyrosine phosphorylation sites remain to be identified. In this study we examined 2 candidate tyrosine residues near the boundary between the first nucleotide binding domain and the R domain, a region which is important for channel function but devoid of PKA consensus sequences. Mutating tyrosines at positions 625 and 627 dramatically reduced responses to Src or Pyk2 without altering the activation by PKA, suggesting they may contribute to CFTR regulation.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"31 1","pages":"247 - 251 - 53"},"PeriodicalIF":3.3,"publicationDate":"2016-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75416155","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}
Pub Date : 2016-01-26DOI: 10.1080/19336950.2015.1121335
M. Vornanen, M. Hassinen
ABSTRACT The zebrafish (Danio rerio) has become a popular model for human cardiac diseases and pharmacology including cardiac arrhythmias and its electrophysiological basis. Notably, the phenotype of zebrafish cardiac action potential is similar to the human cardiac action potential in that both have a long plateau phase. Also the major inward and outward current systems are qualitatively similar in zebrafish and human hearts. However, there are also significant differences in ionic current composition between human and zebrafish hearts, and the molecular basis and pharmacological properties of human and zebrafish cardiac ionic currents differ in several ways. Cardiac ionic currents may be produced by non-orthologous genes in zebrafish and humans, and paralogous gene products of some ion channels are expressed in the zebrafish heart. More research on molecular basis of cardiac ion channels, and regulation and drug sensitivity of the cardiac ionic currents are needed to enable rational use of the zebrafish heart as an electrophysiological model for the human heart.
{"title":"Zebrafish heart as a model for human cardiac electrophysiology","authors":"M. Vornanen, M. Hassinen","doi":"10.1080/19336950.2015.1121335","DOIUrl":"https://doi.org/10.1080/19336950.2015.1121335","url":null,"abstract":"ABSTRACT The zebrafish (Danio rerio) has become a popular model for human cardiac diseases and pharmacology including cardiac arrhythmias and its electrophysiological basis. Notably, the phenotype of zebrafish cardiac action potential is similar to the human cardiac action potential in that both have a long plateau phase. Also the major inward and outward current systems are qualitatively similar in zebrafish and human hearts. However, there are also significant differences in ionic current composition between human and zebrafish hearts, and the molecular basis and pharmacological properties of human and zebrafish cardiac ionic currents differ in several ways. Cardiac ionic currents may be produced by non-orthologous genes in zebrafish and humans, and paralogous gene products of some ion channels are expressed in the zebrafish heart. More research on molecular basis of cardiac ion channels, and regulation and drug sensitivity of the cardiac ionic currents are needed to enable rational use of the zebrafish heart as an electrophysiological model for the human heart.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"5 1","pages":"101 - 110"},"PeriodicalIF":3.3,"publicationDate":"2016-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89350298","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}
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