Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Oberhofer, M; Tian, Q; Ruppenthal, S; Wegener, S; Reil, JC; Körbel, C; Hammer, K; Menger, M; Neuberger, HR; Kaestner, L; Lipp, P.
Calcium dysregulation in ventricular myocytes from mice expressing constitutively active Rac1.
Cell Calcium. 2013; 54(1):26-36 Doi: 10.1016/j.ceca.2013.03.006
Web of Science PubMed FullText FullText_MUG


Co-Autor*innen der Med Uni Graz
Hammer Karin Petra

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Increased Rac1 activity and its concomitant elevation of reactive oxygen species (ROS) levels is believed to be involved in the development of cardiac diseases such as hypertrophy and arrhythmia. To study the effects of activated Rac1 on the properties of isolated ventricular myocytes we used a transgenic mouse model (RacET) expressing constitutively active Rac1. Concurrent with dilated cardiomyopathy global Ca(2+) handling as well as single cell contractility was substantially decreased. Cellular ROS levels were assessed with two independent assays and unexpectedly depicted decreased ROS production in RacET that was uncoupled from hormonal stimulation. Western blot analysis illustrated a massive increase in cellular Rac1 activity concomitant with a reduction in NADPH-oxidase activity. Analysis of the Ca(2+) current, the ryanodine receptor and fractional Ca(2+) release uncovered defective excitation-contraction (ec) coupling and a substantial increase in sarcoplasmic reticulum Ca(2+) leak together with a larger Ca(2+) spark amplitude and frequency. We conclude that Rac1 activity plays an important role for cardiac diseases but can be uncoupled from NADPH-oxidase activity. Rac1-mediated partial uncoupling of the ec-coupling machinery results in a ROS-independent disarrayed cellular Ca(2+) handling, contractility and impaired cardiac function.
Find related publications in this database (using NLM MeSH Indexing)
Action Potentials - physiology
Animals -
Calcium - metabolism
Calcium Channels, L-Type - physiology
Cells, Cultured -
Heart Ventricles - cytology
Male -
Membrane Glycoproteins - metabolism
Mice -
Mice, Transgenic -
Models, Animal -
Myocytes, Cardiac - cytology
NADPH Oxidase - metabolism
Neuropeptides - genetics
Reactive Oxygen Species - metabolism
Sarcoplasmic Reticulum - metabolism
rac1 GTP-Binding Protein - genetics

Find related publications in this database (Keywords)
NADPH oxidase
Reactive oxygen species
Excitation contraction coupling
Calcium handling
Calcium spark
© Med Uni Graz Impressum