U Gergs1, C M Fahrion1, P Bock1, M Fischer1, H Wache1, S Hauptmann2, W Schmitz3, J Neumann1. 1. Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany. 2. Institut für Pathologie am Krankenhaus Düren gGmbH, Düren, Germany. 3. Institut für Pharmakologie und Toxikologie, Universitätsklinikum Münster, Münster, Germany.
Abstract
AIM: Several genetically modified mice models were studied so far to investigate the role of cardiac calsequestrin (CSQ2) for the contractile function of the ventricle and for the occurrence of ventricular tachycardia. Using a CSQ2 knockout mouse, we wanted to study also the atrial function of CSQ2. METHODS: The influence of CSQ2 on atrial function and, for comparison, ventricular function was studied in isolated cardiac preparations and by echocardiography as well as electrocardiography in mice with deletion of CSQ2. RESULTS: Using deletion of exon 1, we have successfully generated a constitutive knockout mouse of the calsequestrin 2 gene (CSQ2-/- ). CSQ2 protein was absent in the heart (atrium, ventricle), but also in oesophagus and skeletal muscle of homozygous knockout mice. In 6-month-old CSQ2-/- mice, relative left atrial weight was increased, whereas relative heart weight was unchanged. The staircase phenomena in paced left atrial preparations on force of contraction and the post-rest potentiation were different between wild type and CSQ2-/- indicative for a decreased sarcoplasmic Ca2+ load and supporting an important role of CSQ2 also in the atrium. The incidence of arrhythmias was increased in CSQ2-/- . In 2-year-old CSQ2-/- mice, cardiac hypertrophy and heart failure were noted possibly as a result of chronically increased cytosolic Ca2+ levels. CONCLUSION: These data suggest a functional role of CSQ2 not only in the ventricle but also in the atrium of mammalian hearts. Loss of CSQ2 function can cause not only arrhythmias, but also cardiac hypertrophy and heart failure.
AIM: Several genetically modified mice models were studied so far to investigate the role of cardiac calsequestrin (CSQ2) for the contractile function of the ventricle and for the occurrence of ventricular tachycardia. Using a CSQ2 knockout mouse, we wanted to study also the atrial function of CSQ2. METHODS: The influence of CSQ2 on atrial function and, for comparison, ventricular function was studied in isolated cardiac preparations and by echocardiography as well as electrocardiography in mice with deletion of CSQ2. RESULTS: Using deletion of exon 1, we have successfully generated a constitutive knockout mouse of the calsequestrin 2 gene (CSQ2-/- ). CSQ2 protein was absent in the heart (atrium, ventricle), but also in oesophagus and skeletal muscle of homozygous knockout mice. In 6-month-old CSQ2-/-mice, relative left atrial weight was increased, whereas relative heart weight was unchanged. The staircase phenomena in paced left atrial preparations on force of contraction and the post-rest potentiation were different between wild type and CSQ2-/- indicative for a decreased sarcoplasmic Ca2+ load and supporting an important role of CSQ2 also in the atrium. The incidence of arrhythmias was increased in CSQ2-/- . In 2-year-old CSQ2-/-mice, cardiac hypertrophy and heart failure were noted possibly as a result of chronically increased cytosolic Ca2+ levels. CONCLUSION: These data suggest a functional role of CSQ2 not only in the ventricle but also in the atrium of mammalian hearts. Loss of CSQ2 function can cause not only arrhythmias, but also cardiac hypertrophy and heart failure.
Authors: Thorsten Krause; Stefanie Grote-Wessels; Felix Balzer; Peter Boknik; Ulrich Gergs; Uwe Kirchhefer; Igor B Buchwalow; Frank U Müller; Wilhelm Schmitz; Joachim Neumann Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2018-05-24 Impact factor: 3.000
Authors: Ulrich Gergs; Timo Gerigk; Jonas Wittschier; Constanze T Schmidbaur; Clara Röttger; Mareen Mahnkopf; Hanna Edler; Hartmut Wache; Joachim Neumann Journal: Biomedicines Date: 2021-05-18