Pub Date : 2016-01-08DOI: 10.1080/19336950.2015.1137176
Tatiana Kilch, S. Kappel, C. Peinelt
AbstractPrecise intracellular Ca2+ signaling is crucial to ensure proper cellular functions. Subsequently, imbalances in Ca2+ signaling, particularly in store-operated Ca2+ entry (SOCE), contribute to several pathophysiological malfunctions in immune diseases and cancer. We lately reported on heteromeric Orai1/Orai3 SOCE channels and transient receptor potential melastatin-4 (TRPM4) channels in prostate cancer cells. We here sum up our findings and provide a model for the regulation of Ca2+ signaling in prostate cancer cells.
{"title":"Regulation of Ca2+ signaling in prostate cancer cells","authors":"Tatiana Kilch, S. Kappel, C. Peinelt","doi":"10.1080/19336950.2015.1137176","DOIUrl":"https://doi.org/10.1080/19336950.2015.1137176","url":null,"abstract":"AbstractPrecise intracellular Ca2+ signaling is crucial to ensure proper cellular functions. Subsequently, imbalances in Ca2+ signaling, particularly in store-operated Ca2+ entry (SOCE), contribute to several pathophysiological malfunctions in immune diseases and cancer. We lately reported on heteromeric Orai1/Orai3 SOCE channels and transient receptor potential melastatin-4 (TRPM4) channels in prostate cancer cells. We here sum up our findings and provide a model for the regulation of Ca2+ signaling in prostate cancer cells.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"121 1","pages":"170 - 171"},"PeriodicalIF":3.3,"publicationDate":"2016-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74276644","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 : 2016-01-05DOI: 10.1080/19336950.2015.1116652
K. Bertram, U. Banderali, P. Tailor, R. Krawetz
ABSTRACT Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.
{"title":"Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells","authors":"K. Bertram, U. Banderali, P. Tailor, R. Krawetz","doi":"10.1080/19336950.2015.1116652","DOIUrl":"https://doi.org/10.1080/19336950.2015.1116652","url":null,"abstract":"ABSTRACT Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"11 1","pages":"148 - 157"},"PeriodicalIF":3.3,"publicationDate":"2016-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78116434","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 : 2016-01-02DOI: 10.1080/19336950.2015.1108499
Adva Benmocha Guggenheimer, L. Almagor, V. Tsemakhovich, D. R. Tripathy, J. Hirsch, N. Dascal
The modulation and regulation of voltage-gated Ca2+ channels is affected by the pore-forming segments, the cytosolic parts of the channel, and interacting intracellular proteins. In this study we demonstrate a direct physical interaction between the N terminus (NT) and C terminus (CT) of the main subunit of the L-type Ca2+ channel CaV1.2, α1C, and explore the importance of this interaction for the regulation of the channel. We used biochemistry to measure the strength of the interaction and to map the location of the interaction sites, and electrophysiology to investigate the functional impact of the interaction. We show that the full-length NT (amino acids 1-154) and the proximal (close to the plasma membrane) part of the CT, pCT (amino acids 1508-1669) interact with sub-micromolar to low-micromolar affinity. Calmodulin (CaM) is not essential for the binding. The results further suggest that the NT-CT interaction regulates the channel's inactivation, and that Ca2+, presumably through binding to calmodulin (CaM), reduces the strength of NT-CT interaction. We propose a molecular mechanism in which NT and CT of the channel serve as levers whose movements regulate inactivation by promoting changes in the transmembrane core of the channel via S1 (NT) or S6 (pCT) segments of domains I and IV, accordingly, and not as a kind of pore blocker. We hypothesize that Ca2+-CaM-induced changes in NT-CT interaction may, in part, underlie the acceleration of CaV1.2 inactivation induced by Ca2+ entry into the cell.
{"title":"Interactions between N and C termini of α1C subunit regulate inactivation of CaV1.2 L-type Ca2+ channel","authors":"Adva Benmocha Guggenheimer, L. Almagor, V. Tsemakhovich, D. R. Tripathy, J. Hirsch, N. Dascal","doi":"10.1080/19336950.2015.1108499","DOIUrl":"https://doi.org/10.1080/19336950.2015.1108499","url":null,"abstract":"The modulation and regulation of voltage-gated Ca2+ channels is affected by the pore-forming segments, the cytosolic parts of the channel, and interacting intracellular proteins. In this study we demonstrate a direct physical interaction between the N terminus (NT) and C terminus (CT) of the main subunit of the L-type Ca2+ channel CaV1.2, α1C, and explore the importance of this interaction for the regulation of the channel. We used biochemistry to measure the strength of the interaction and to map the location of the interaction sites, and electrophysiology to investigate the functional impact of the interaction. We show that the full-length NT (amino acids 1-154) and the proximal (close to the plasma membrane) part of the CT, pCT (amino acids 1508-1669) interact with sub-micromolar to low-micromolar affinity. Calmodulin (CaM) is not essential for the binding. The results further suggest that the NT-CT interaction regulates the channel's inactivation, and that Ca2+, presumably through binding to calmodulin (CaM), reduces the strength of NT-CT interaction. We propose a molecular mechanism in which NT and CT of the channel serve as levers whose movements regulate inactivation by promoting changes in the transmembrane core of the channel via S1 (NT) or S6 (pCT) segments of domains I and IV, accordingly, and not as a kind of pore blocker. We hypothesize that Ca2+-CaM-induced changes in NT-CT interaction may, in part, underlie the acceleration of CaV1.2 inactivation induced by Ca2+ entry into the cell.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"13 1","pages":"55 - 68"},"PeriodicalIF":3.3,"publicationDate":"2016-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82356602","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}
This essay explores feminism, socially-constructed norms, and the relationship between feminism and technical communication. It argues that undergraduate technical communication programs should include courses that study feminist history and theories as related to the field, claiming that studying feminist theory will improve user-centered design and broaden students' spheres of influence as professionals.
{"title":"Feminist Theory and Technical Communication","authors":"Olivia Duffus","doi":"10.15385/JCH.2016.1.1.5","DOIUrl":"https://doi.org/10.15385/JCH.2016.1.1.5","url":null,"abstract":"This essay explores feminism, socially-constructed norms, and the relationship between feminism and technical communication. It argues that undergraduate technical communication programs should include courses that study feminist history and theories as related to the field, claiming that studying feminist theory will improve user-centered design and broaden students' spheres of influence as professionals.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"1 1","pages":"5"},"PeriodicalIF":3.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78189685","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}
Abstract The development of modern technology has increasingly focused on efficiency over expression. Interfaces limit and scale down human choice and expression. Entertainment and communication now use interfaced technology for even basic human expression, artificially limiting the number of potential choices to the options presented by the interface. The logic of technology has become a totalizing phenomenon, bringing all areas of human life under it purview. According to Heidegger, Ellul, and Flusser, the result of this development is a different way of being-in-the-world for humans. The traditional man has been the constant in production and communication, which the medium and technology have been the variable. The modern man has reversed his orientation towards technology, the man is the variable and the machine is the constant. Building machines no longer appears to serve humanity, but instead has become an end in itself. Due to the methods of technology and quantification of nearly every decision, free choice is becoming more and more difficult to comprehend. As a case study for these arguments, The Stanley Parable examines how media can be used to limit possible choices, and can also be used to encourage new forms of play that counteract the predictability of machines and technical communication through human expression and increased computer literacy.
{"title":"Choosing to Choose: The Impact of Technology on Choice","authors":"Aaron J. Alford","doi":"10.15385/JCH.2016.1.1.8","DOIUrl":"https://doi.org/10.15385/JCH.2016.1.1.8","url":null,"abstract":"Abstract The development of modern technology has increasingly focused on efficiency over expression. Interfaces limit and scale down human choice and expression. Entertainment and communication now use interfaced technology for even basic human expression, artificially limiting the number of potential choices to the options presented by the interface. The logic of technology has become a totalizing phenomenon, bringing all areas of human life under it purview. According to Heidegger, Ellul, and Flusser, the result of this development is a different way of being-in-the-world for humans. The traditional man has been the constant in production and communication, which the medium and technology have been the variable. The modern man has reversed his orientation towards technology, the man is the variable and the machine is the constant. Building machines no longer appears to serve humanity, but instead has become an end in itself. Due to the methods of technology and quantification of nearly every decision, free choice is becoming more and more difficult to comprehend. As a case study for these arguments, The Stanley Parable examines how media can be used to limit possible choices, and can also be used to encourage new forms of play that counteract the predictability of machines and technical communication through human expression and increased computer literacy.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"8 1","pages":"8"},"PeriodicalIF":3.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81697707","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}
Jared L. Newman, Luke M. Tomlinson, Grayson H. Dearing, F. Harmon
Motivated by high energy costs, people and organizations want to cut back on their energy consumption. However, the only feedback consumers typically receive is a monthly bill listing their total electricity usage (in kWh). Some companies have begun developing systems that allow households and organizations to monitor their energy usage for individual circuits. Available systems are expensive so a CU engineering senior design team has designed, fabricated, and tested a system for use at Cedarville University. The AC power monitoring system has the ability to measure energy consumption for each individual circuit in the breaker panel, store the data, and then provide the user with visual feedback on energy usage behavior. The basic system provides the proof of concept for future senior design teams. After more testing is completed, further development of this product will be needed by other senior design teams. Eventually, this energy monitoring system could be expanded to include larger loads such as HVAC systems and refrigeration units. It is also envisioned that future projects might be able to provide the user with suggestions for changing and improving energy usage behavior. Failure prediction of equipment on individual circuits could also stem from this initial project. For this project, it has been clearly shown that the concept is feasible, expandable, and cost-effective.
{"title":"AC Power Monitoring System","authors":"Jared L. Newman, Luke M. Tomlinson, Grayson H. Dearing, F. Harmon","doi":"10.15385/jch.2016.1.1.7","DOIUrl":"https://doi.org/10.15385/jch.2016.1.1.7","url":null,"abstract":"Motivated by high energy costs, people and organizations want to cut back on their energy consumption. However, the only feedback consumers typically receive is a monthly bill listing their total electricity usage (in kWh). Some companies have begun developing systems that allow households and organizations to monitor their energy usage for individual circuits. Available systems are expensive so a CU engineering senior design team has designed, fabricated, and tested a system for use at Cedarville University. The AC power monitoring system has the ability to measure energy consumption for each individual circuit in the breaker panel, store the data, and then provide the user with visual feedback on energy usage behavior. The basic system provides the proof of concept for future senior design teams. After more testing is completed, further development of this product will be needed by other senior design teams. Eventually, this energy monitoring system could be expanded to include larger loads such as HVAC systems and refrigeration units. It is also envisioned that future projects might be able to provide the user with suggestions for changing and improving energy usage behavior. Failure prediction of equipment on individual circuits could also stem from this initial project. For this project, it has been clearly shown that the concept is feasible, expandable, and cost-effective.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"26 1","pages":"7"},"PeriodicalIF":3.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84818114","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}
The Pauline doctrine of justification is a prevailing subject among biblical scholarship today. Especially, as a New Perspective on Pauline literature rises claiming that Luther was wrong in his view of Justification, since he was blinded by his own context forcing it into his interpretation of the Pauline text. Consequently, the reformed view cannot be right since it interprets the doctrine of justification mainly through soteriological lens, whereas the Apostle had only ecclesiological purposes in mind when addressing the subject. In light of the previous thought, the purpose of the article is to criticize the New Perspective’s exclusive method by proposing a “both-end” approach to Justification affirming the soteriological aspects of justification held by Luther, but also pointing out the reality of ecclesiological implications. The article is divided in two main sections. The first section highlights the NPP (New Perspective on Paul) definitions of key terms, such as “Works of the Law”, “the Righteousness of God”, and “Justification”, followed by important observations concerning their view of the terms. The second portion of the article provides three main arguments for Paul’s use of the doctrine of Justification having primarily in mind soteriological purposes. The hope for this work is not to solve the debate between both parties, but to demonstrate that the traditional (reformed) view concerning the doctrine of justification is not absurd, as some would say, and that it is possible to hold a soteriological position and still affirm ecclesiological implications to the Pauline doctrine.
{"title":"Justification by Faith: A \"Both-And\" Approach","authors":"Rodrigo N Reis","doi":"10.15385/JCH.2016.1.1.1","DOIUrl":"https://doi.org/10.15385/JCH.2016.1.1.1","url":null,"abstract":"The Pauline doctrine of justification is a prevailing subject among biblical scholarship today. Especially, as a New Perspective on Pauline literature rises claiming that Luther was wrong in his view of Justification, since he was blinded by his own context forcing it into his interpretation of the Pauline text. Consequently, the reformed view cannot be right since it interprets the doctrine of justification mainly through soteriological lens, whereas the Apostle had only ecclesiological purposes in mind when addressing the subject. In light of the previous thought, the purpose of the article is to criticize the New Perspective’s exclusive method by proposing a “both-end” approach to Justification affirming the soteriological aspects of justification held by Luther, but also pointing out the reality of ecclesiological implications. The article is divided in two main sections. The first section highlights the NPP (New Perspective on Paul) definitions of key terms, such as “Works of the Law”, “the Righteousness of God”, and “Justification”, followed by important observations concerning their view of the terms. The second portion of the article provides three main arguments for Paul’s use of the doctrine of Justification having primarily in mind soteriological purposes. The hope for this work is not to solve the debate between both parties, but to demonstrate that the traditional (reformed) view concerning the doctrine of justification is not absurd, as some would say, and that it is possible to hold a soteriological position and still affirm ecclesiological implications to the Pauline doctrine.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"20 1","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90254549","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}
We live in a visual age in which we find visual information surrounding us on every side. The persuasive power of the visual has long been recognized by scholars, but there is a lack of emphasis in the classroom on how to effectively create an effectively persuasive visual. Professors at the collegiate level need to teach their students to be visually literate, to make them responsible users and creators of images.
{"title":"Visual Rhetoric: A Case for Visual Literacy in the Classroom","authors":"Kaitlyn J Tomlinson","doi":"10.15385/JCH.2016.1.1.9","DOIUrl":"https://doi.org/10.15385/JCH.2016.1.1.9","url":null,"abstract":"We live in a visual age in which we find visual information surrounding us on every side. The persuasive power of the visual has long been recognized by scholars, but there is a lack of emphasis in the classroom on how to effectively create an effectively persuasive visual. Professors at the collegiate level need to teach their students to be visually literate, to make them responsible users and creators of images.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"20 1","pages":"9"},"PeriodicalIF":3.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78237243","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 : 2015-12-08DOI: 10.1080/19336950.2015.1120390
Victoria A. Baronas, Runying Yang, Y. Vilin, Harley T. Kurata
ABSTRACT Voltage-gated potassium channels are important regulators of electrical excitation in many tissues, with Kv1.2 standing out as an essential contributor in the CNS. Genetic deletion of Kv1.2 invariably leads to early lethality in mice. In humans, mutations affecting Kv1.2 function are linked to epileptic encephalopathy and movement disorders. We have demonstrated that Kv1.2 is subject to a unique regulatory mechanism in which repetitive stimulation leads to dramatic potentiation of current. In this study, we explore the properties and molecular determinants of this use-dependent potentiation/activation. First, we examine how alterations in duty cycle (depolarization and repolarization/recovery times) affect the onset and extent of use-dependent activation. Also, we use trains of repetitive depolarizations to test the effects of a variety of Thr252 (S2-S3 linker) mutations on use-dependent activation. Substitutions of Thr with some sterically similar amino acids (Ser, Val, and Met, but not Cys) retain use-dependent activation, while bulky or charged amino acid substitutions eliminate use-dependence. Introduction of Thr at the equivalent position in other Kv1 channels (1.1, 1.3, 1.4), was not sufficient to transfer the phenotype. We hypothesize that use-dependent activation of Kv1.2 channels is mediated by an extrinsic regulator that binds preferentially to the channel closed state, with Thr252 being necessary but not sufficient for this interaction to alter channel function. These findings extend the conclusions of our recent demonstration of use-dependent activation of Kv1.2-containing channels in hippocampal neurons, by adding new details about the molecular mechanism underlying this effect.
{"title":"Determinants of frequency-dependent regulation of Kv1.2-containing potassium channels","authors":"Victoria A. Baronas, Runying Yang, Y. Vilin, Harley T. Kurata","doi":"10.1080/19336950.2015.1120390","DOIUrl":"https://doi.org/10.1080/19336950.2015.1120390","url":null,"abstract":"ABSTRACT Voltage-gated potassium channels are important regulators of electrical excitation in many tissues, with Kv1.2 standing out as an essential contributor in the CNS. Genetic deletion of Kv1.2 invariably leads to early lethality in mice. In humans, mutations affecting Kv1.2 function are linked to epileptic encephalopathy and movement disorders. We have demonstrated that Kv1.2 is subject to a unique regulatory mechanism in which repetitive stimulation leads to dramatic potentiation of current. In this study, we explore the properties and molecular determinants of this use-dependent potentiation/activation. First, we examine how alterations in duty cycle (depolarization and repolarization/recovery times) affect the onset and extent of use-dependent activation. Also, we use trains of repetitive depolarizations to test the effects of a variety of Thr252 (S2-S3 linker) mutations on use-dependent activation. Substitutions of Thr with some sterically similar amino acids (Ser, Val, and Met, but not Cys) retain use-dependent activation, while bulky or charged amino acid substitutions eliminate use-dependence. Introduction of Thr at the equivalent position in other Kv1 channels (1.1, 1.3, 1.4), was not sufficient to transfer the phenotype. We hypothesize that use-dependent activation of Kv1.2 channels is mediated by an extrinsic regulator that binds preferentially to the channel closed state, with Thr252 being necessary but not sufficient for this interaction to alter channel function. These findings extend the conclusions of our recent demonstration of use-dependent activation of Kv1.2-containing channels in hippocampal neurons, by adding new details about the molecular mechanism underlying this effect.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"7 1","pages":"158 - 166"},"PeriodicalIF":3.3,"publicationDate":"2015-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89825087","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 : 2015-11-02DOI: 10.1080/19336950.2015.1081725
A. Gerlach, Brett M. Antonio
A prerequisite for a successful target-based drug discovery program is a robust data set that increases confidence in the validation of the molecular target and the therapeutic approach. Given the significant time and resource investment required to carry a drug to market, early selection of targets that can be modulated safely and effectively forms the basis for a strong portfolio and pipeline. In this article we present some of the more useful scientific approaches that can be applied toward the validation of ion channel targets, a molecular family with a history of clinical success in therapeutic areas such as cardiovascular, respiratory, pain and neuroscience.
{"title":"Validation of ion channel targets","authors":"A. Gerlach, Brett M. Antonio","doi":"10.1080/19336950.2015.1081725","DOIUrl":"https://doi.org/10.1080/19336950.2015.1081725","url":null,"abstract":"A prerequisite for a successful target-based drug discovery program is a robust data set that increases confidence in the validation of the molecular target and the therapeutic approach. Given the significant time and resource investment required to carry a drug to market, early selection of targets that can be modulated safely and effectively forms the basis for a strong portfolio and pipeline. In this article we present some of the more useful scientific approaches that can be applied toward the validation of ion channel targets, a molecular family with a history of clinical success in therapeutic areas such as cardiovascular, respiratory, pain and neuroscience.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"9 1","pages":"376 - 379"},"PeriodicalIF":3.3,"publicationDate":"2015-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87464204","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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