Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes
Background/Aims: Dysferlin plays a decisive role in calcium-dependent membrane repair in myocytes. Mutations in the encoding DYSF gene cause a number of myopathies, e.g. limb-girdle muscular dystrophy type 2B (LGMD2B). Besides skeletal muscle degenerative processes, dysferlin deficiency is also asso...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2015-06-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/430278 |
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| author | Lena Rubi Vaibhavkumar S. Gawali Helmut Kubista Hannes Todt Karlheinz Hilber Xaver Koenig |
| author_facet | Lena Rubi Vaibhavkumar S. Gawali Helmut Kubista Hannes Todt Karlheinz Hilber Xaver Koenig |
| author_sort | Lena Rubi |
| collection | DOAJ |
| description | Background/Aims: Dysferlin plays a decisive role in calcium-dependent membrane repair in myocytes. Mutations in the encoding DYSF gene cause a number of myopathies, e.g. limb-girdle muscular dystrophy type 2B (LGMD2B). Besides skeletal muscle degenerative processes, dysferlin deficiency is also associated with cardiac complications. Thus, both LGMD2B patients and dysferlin-deficient mice develop a dilated cardiomyopathy. We and others have recently reported that dystrophin-deficient ventricular cardiomyocytes from mouse models of Duchenne muscular dystrophy show significant abnormalities in voltage-dependent ion channels, which may contribute to the pathophysiology in dystrophic cardiomyopathy. The aim of the present study was to investigate if dysferlin, like dystrophin, is a regulator of cardiac ion channels. Methods and Results: By using the whole cell patch-clamp technique, we compared the properties of voltage-dependent calcium and sodium channels, as well as action potentials in ventricular cardiomyocytes isolated from the hearts of normal and dysferlin-deficient (dysf) mice. In contrast to dystrophin deficiency, the lack of dysferlin did not impair the ion channel properties and left action potential parameters unaltered. In connection with normal ECGs in dysf mice these results suggest that dysferlin deficiency does not perturb cardiac electrophysiology. Conclusion: Our study demonstrates that dysferlin does not regulate cardiac voltage-dependent ion channels, and implies that abnormalities in cardiac ion channels are not a universal characteristic of all muscular dystrophy types. |
| first_indexed | 2024-12-12T09:58:25Z |
| format | Article |
| id | doaj.art-9143b3070de14c07b2462544ab1ef1d3 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-12T09:58:25Z |
| publishDate | 2015-06-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-9143b3070de14c07b2462544ab1ef1d32022-12-22T00:28:04ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-06-013631049105810.1159/000430278430278Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient CardiomyocytesLena RubiVaibhavkumar S. GawaliHelmut KubistaHannes TodtKarlheinz HilberXaver KoenigBackground/Aims: Dysferlin plays a decisive role in calcium-dependent membrane repair in myocytes. Mutations in the encoding DYSF gene cause a number of myopathies, e.g. limb-girdle muscular dystrophy type 2B (LGMD2B). Besides skeletal muscle degenerative processes, dysferlin deficiency is also associated with cardiac complications. Thus, both LGMD2B patients and dysferlin-deficient mice develop a dilated cardiomyopathy. We and others have recently reported that dystrophin-deficient ventricular cardiomyocytes from mouse models of Duchenne muscular dystrophy show significant abnormalities in voltage-dependent ion channels, which may contribute to the pathophysiology in dystrophic cardiomyopathy. The aim of the present study was to investigate if dysferlin, like dystrophin, is a regulator of cardiac ion channels. Methods and Results: By using the whole cell patch-clamp technique, we compared the properties of voltage-dependent calcium and sodium channels, as well as action potentials in ventricular cardiomyocytes isolated from the hearts of normal and dysferlin-deficient (dysf) mice. In contrast to dystrophin deficiency, the lack of dysferlin did not impair the ion channel properties and left action potential parameters unaltered. In connection with normal ECGs in dysf mice these results suggest that dysferlin deficiency does not perturb cardiac electrophysiology. Conclusion: Our study demonstrates that dysferlin does not regulate cardiac voltage-dependent ion channels, and implies that abnormalities in cardiac ion channels are not a universal characteristic of all muscular dystrophy types.http://www.karger.com/Article/FullText/430278Dysferlin deficiencyVentricular cardiomyocytesLimb-girdle muscular dystrophy type 2BL-type calcium channelMouse modelVoltage-dependent ion channelsDilated cardiomyopathy |
| spellingShingle | Lena Rubi Vaibhavkumar S. Gawali Helmut Kubista Hannes Todt Karlheinz Hilber Xaver Koenig Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes Cellular Physiology and Biochemistry Dysferlin deficiency Ventricular cardiomyocytes Limb-girdle muscular dystrophy type 2B L-type calcium channel Mouse model Voltage-dependent ion channels Dilated cardiomyopathy |
| title | Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes |
| title_full | Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes |
| title_fullStr | Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes |
| title_full_unstemmed | Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes |
| title_short | Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes |
| title_sort | proper voltage dependent ion channel function in dysferlin deficient cardiomyocytes |
| topic | Dysferlin deficiency Ventricular cardiomyocytes Limb-girdle muscular dystrophy type 2B L-type calcium channel Mouse model Voltage-dependent ion channels Dilated cardiomyopathy |
| url | http://www.karger.com/Article/FullText/430278 |
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