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Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats
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Zeitschriftentitel: | Circulation Research |
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Personen und Körperschaften: | , , , , , , , , , , , , , , , , , |
In: | Circulation Research, 83, 1998, 9, S. 877-888 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Ovid Technologies (Wolters Kluwer Health)
|
Schlagwörter: |
author_facet |
Hammes, Annette Oberdorf-Maass, Silke Rother, Tobias Nething, Katja Gollnick, Frank Linz, Klaus W. Meyer, Rainer Hu, Kai Han, Hong Gaudron, Peter Ertl, Georg Hoffmann, Sigrid Ganten, Ursula Vetter, Roland Schuh, Kai Benkwitz, Claudia Zimmer, Hans G. Neyses, Ludwig Hammes, Annette Oberdorf-Maass, Silke Rother, Tobias Nething, Katja Gollnick, Frank Linz, Klaus W. Meyer, Rainer Hu, Kai Han, Hong Gaudron, Peter Ertl, Georg Hoffmann, Sigrid Ganten, Ursula Vetter, Roland Schuh, Kai Benkwitz, Claudia Zimmer, Hans G. Neyses, Ludwig |
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author |
Hammes, Annette Oberdorf-Maass, Silke Rother, Tobias Nething, Katja Gollnick, Frank Linz, Klaus W. Meyer, Rainer Hu, Kai Han, Hong Gaudron, Peter Ertl, Georg Hoffmann, Sigrid Ganten, Ursula Vetter, Roland Schuh, Kai Benkwitz, Claudia Zimmer, Hans G. Neyses, Ludwig |
spellingShingle |
Hammes, Annette Oberdorf-Maass, Silke Rother, Tobias Nething, Katja Gollnick, Frank Linz, Klaus W. Meyer, Rainer Hu, Kai Han, Hong Gaudron, Peter Ertl, Georg Hoffmann, Sigrid Ganten, Ursula Vetter, Roland Schuh, Kai Benkwitz, Claudia Zimmer, Hans G. Neyses, Ludwig Circulation Research Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats Cardiology and Cardiovascular Medicine Physiology |
author_sort |
hammes, annette |
spelling |
Hammes, Annette Oberdorf-Maass, Silke Rother, Tobias Nething, Katja Gollnick, Frank Linz, Klaus W. Meyer, Rainer Hu, Kai Han, Hong Gaudron, Peter Ertl, Georg Hoffmann, Sigrid Ganten, Ursula Vetter, Roland Schuh, Kai Benkwitz, Claudia Zimmer, Hans G. Neyses, Ludwig 0009-7330 1524-4571 Ovid Technologies (Wolters Kluwer Health) Cardiology and Cardiovascular Medicine Physiology http://dx.doi.org/10.1161/01.res.83.9.877 <jats:p> <jats:italic>Abstract</jats:italic> —The plasma membrane calmodulin–dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca <jats:sup>2+</jats:sup> homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na <jats:sup>+</jats:sup> /Ca <jats:sup>2+</jats:sup> exchanger. We approached the question of the physiological function of the calcium pump using a transgenic “gain of function” model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the <jats:sc>L</jats:sc> -type Ca <jats:sup>2+</jats:sup> current, or fast [Ca <jats:sup>2+</jats:sup> ] <jats:sub>i</jats:sub> transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 μmol/L phenylephrine. A 1.4-fold– and 2.0-fold–higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the α- and β-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of α- and β-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca <jats:sup>2+</jats:sup> -pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction. </jats:p> Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats Circulation Research |
doi_str_mv |
10.1161/01.res.83.9.877 |
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Online Free |
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Medizin Biologie |
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ElectronicArticle |
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1998 |
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Circulation Research |
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title |
Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_unstemmed |
Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_full |
Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_fullStr |
Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_full_unstemmed |
Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_short |
Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_sort |
overexpression of the sarcolemmal calcium pump in the myocardium of transgenic rats |
topic |
Cardiology and Cardiovascular Medicine Physiology |
url |
http://dx.doi.org/10.1161/01.res.83.9.877 |
publishDate |
1998 |
physical |
877-888 |
description |
<jats:p>
<jats:italic>Abstract</jats:italic>
—The plasma membrane calmodulin–dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca
<jats:sup>2+</jats:sup>
homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na
<jats:sup>+</jats:sup>
/Ca
<jats:sup>2+</jats:sup>
exchanger. We approached the question of the physiological function of the calcium pump using a transgenic “gain of function” model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the
<jats:sc>L</jats:sc>
-type Ca
<jats:sup>2+</jats:sup>
current, or fast [Ca
<jats:sup>2+</jats:sup>
]
<jats:sub>i</jats:sub>
transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 μmol/L phenylephrine. A 1.4-fold– and 2.0-fold–higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the α- and β-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of α- and β-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca
<jats:sup>2+</jats:sup>
-pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction.
</jats:p> |
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author | Hammes, Annette, Oberdorf-Maass, Silke, Rother, Tobias, Nething, Katja, Gollnick, Frank, Linz, Klaus W., Meyer, Rainer, Hu, Kai, Han, Hong, Gaudron, Peter, Ertl, Georg, Hoffmann, Sigrid, Ganten, Ursula, Vetter, Roland, Schuh, Kai, Benkwitz, Claudia, Zimmer, Hans G., Neyses, Ludwig |
author_facet | Hammes, Annette, Oberdorf-Maass, Silke, Rother, Tobias, Nething, Katja, Gollnick, Frank, Linz, Klaus W., Meyer, Rainer, Hu, Kai, Han, Hong, Gaudron, Peter, Ertl, Georg, Hoffmann, Sigrid, Ganten, Ursula, Vetter, Roland, Schuh, Kai, Benkwitz, Claudia, Zimmer, Hans G., Neyses, Ludwig, Hammes, Annette, Oberdorf-Maass, Silke, Rother, Tobias, Nething, Katja, Gollnick, Frank, Linz, Klaus W., Meyer, Rainer, Hu, Kai, Han, Hong, Gaudron, Peter, Ertl, Georg, Hoffmann, Sigrid, Ganten, Ursula, Vetter, Roland, Schuh, Kai, Benkwitz, Claudia, Zimmer, Hans G., Neyses, Ludwig |
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description | <jats:p> <jats:italic>Abstract</jats:italic> —The plasma membrane calmodulin–dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca <jats:sup>2+</jats:sup> homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na <jats:sup>+</jats:sup> /Ca <jats:sup>2+</jats:sup> exchanger. We approached the question of the physiological function of the calcium pump using a transgenic “gain of function” model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the <jats:sc>L</jats:sc> -type Ca <jats:sup>2+</jats:sup> current, or fast [Ca <jats:sup>2+</jats:sup> ] <jats:sub>i</jats:sub> transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 μmol/L phenylephrine. A 1.4-fold– and 2.0-fold–higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the α- and β-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of α- and β-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca <jats:sup>2+</jats:sup> -pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction. </jats:p> |
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spelling | Hammes, Annette Oberdorf-Maass, Silke Rother, Tobias Nething, Katja Gollnick, Frank Linz, Klaus W. Meyer, Rainer Hu, Kai Han, Hong Gaudron, Peter Ertl, Georg Hoffmann, Sigrid Ganten, Ursula Vetter, Roland Schuh, Kai Benkwitz, Claudia Zimmer, Hans G. Neyses, Ludwig 0009-7330 1524-4571 Ovid Technologies (Wolters Kluwer Health) Cardiology and Cardiovascular Medicine Physiology http://dx.doi.org/10.1161/01.res.83.9.877 <jats:p> <jats:italic>Abstract</jats:italic> —The plasma membrane calmodulin–dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca <jats:sup>2+</jats:sup> homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na <jats:sup>+</jats:sup> /Ca <jats:sup>2+</jats:sup> exchanger. We approached the question of the physiological function of the calcium pump using a transgenic “gain of function” model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the <jats:sc>L</jats:sc> -type Ca <jats:sup>2+</jats:sup> current, or fast [Ca <jats:sup>2+</jats:sup> ] <jats:sub>i</jats:sub> transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 μmol/L phenylephrine. A 1.4-fold– and 2.0-fold–higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the α- and β-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of α- and β-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca <jats:sup>2+</jats:sup> -pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction. </jats:p> Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats Circulation Research |
spellingShingle | Hammes, Annette, Oberdorf-Maass, Silke, Rother, Tobias, Nething, Katja, Gollnick, Frank, Linz, Klaus W., Meyer, Rainer, Hu, Kai, Han, Hong, Gaudron, Peter, Ertl, Georg, Hoffmann, Sigrid, Ganten, Ursula, Vetter, Roland, Schuh, Kai, Benkwitz, Claudia, Zimmer, Hans G., Neyses, Ludwig, Circulation Research, Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats, Cardiology and Cardiovascular Medicine, Physiology |
title | Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_full | Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_fullStr | Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_full_unstemmed | Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_short | Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
title_sort | overexpression of the sarcolemmal calcium pump in the myocardium of transgenic rats |
title_unstemmed | Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats |
topic | Cardiology and Cardiovascular Medicine, Physiology |
url | http://dx.doi.org/10.1161/01.res.83.9.877 |