دورية أكاديمية
Andersen’s syndrome mutants produce a knockdown of inwardly rectifying K+ channel in mouse skeletal muscle in vivo
| العنوان: | Andersen’s syndrome mutants produce a knockdown of inwardly rectifying K+ channel in mouse skeletal muscle in vivo |
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| المؤلفون: | Simkin, Dina, Robin, Gaëlle, Giuliano, Serena, Vukolic, Ana, Moceri, Pamela, Guy, Nicolas, Wagner, Kay-Dietrich, Lacampagne, Alain, Allard, Bruno, Bendahhou, Saïd |
| المساهمون: | Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA), Northwestern University Evanston, Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology Zürich (ETH Zürich), Hôpital Pasteur Nice (CHU), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Physiologie & médecine expérimentale du Cœur et des Muscles U 1046 (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC) |
| المصدر: | ISSN: 0302-766X. |
| بيانات النشر: | HAL CCSD Springer Verlag |
| سنة النشر: | 2018 |
| المجموعة: | HAL Lyon 1 (University Claude Bernard Lyon 1) |
| مصطلحات موضوعية: | Andersen’s syndrome, Skeletal muscle, Adenovirus, Channelopathies, KIR2.1, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | International audience ; Andersen's syndrome (AS) is a rare autosomal disorder that has been defined by the triad of periodic paralysis, cardiac arrhythmia, and developmental anomalies. AS has been directly linked to over 40 different autosomal dominant negative loss-of-function mutations in the KCNJ2 gene, encoding for the tetrameric strong inward rectifying K+ channel KIR2.1. While KIR2.1 channels have been suggested to contribute to setting the resting membrane potential (RMP) and to control the duration of the action potential (AP) in skeletal and cardiac muscle, the mechanism by which AS mutations produce such complex pathophysiological symptoms is poorly understood. Thus, we use an adenoviral transduction strategy to study in vivo subcellular distribution of wild-type (WT) and AS-associated mutant KIR2.1 channels in mouse skeletal muscle. We determined that WT and D71V AS mutant KIR2.1 channels are localized to the sarcolemma and the transverse tubules (T-tubules) of skeletal muscle fibers, while the ∆314-315 AS KIR2.1 mutation prevents proper trafficking of the homo- or hetero-meric channel complexes. Whole-cell voltage-clamp recordings in individual skeletal muscle fibers confirmed the reduction of inwardly rectifying K+ current (IK1) after transduction with ∆314-315 KIR2.1 as compared to WT channels. Analysis of skeletal muscle function revealed reduced force generation during isometric contraction as well as reduced resistance to muscle fatigue in extensor digitorum longus muscles transduced with AS mutant KIR2.1. Together, these results suggest that KIR2.1 channels may be involved in the excitation-contraction coupling process required for proper skeletal muscle function. Our findings provide clues to mechanisms associated with periodic paralysis in AS. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/29018970; hal-01796153; https://hal.umontpellier.fr/hal-01796153Test; https://hal.umontpellier.fr/hal-01796153/documentTest; https://hal.umontpellier.fr/hal-01796153/file/2018%20Simkim%20et%20al.,%20Andersen%27s%20syndrome.pdfTest; PUBMED: 29018970 |
| DOI: | 10.1007/s00441-017-2696-7 |
| الإتاحة: | https://doi.org/10.1007/s00441-017-2696-7Test https://hal.umontpellier.fr/hal-01796153Test https://hal.umontpellier.fr/hal-01796153/documentTest https://hal.umontpellier.fr/hal-01796153/file/2018%20Simkim%20et%20al.,%20Andersen%27s%20syndrome.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.254D44D0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00441-017-2696-7 |
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