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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2014

AutorInnen: Koenig, X; Rubi, L; Obermair, GJ; Cervenka, R; Dang, XB; Lukacs, P; Kummer, S; Bittner, RE; Kubista, H; Todt, H; Hilber, K

Titel: Enhanced currents through L-type calcium channels in cardiomyocytes disturb the electrophysiology of the dystrophic heart.

Quelle: Am J Physiol Heart Circ Physiol. 2014; 306(4):H564-H573



Autor/innen der Vetmeduni Vienna:

Kummer Stefan

Diese Publikation wurde nicht im Namen der Vetmeduni Vienna erstellt und ist deshalb ausschließlich der persönlichen Publikationsliste des/der Autors/Autorin zugeordnet!


Abstract:
Duchenne muscular dystrophy (DMD), induced by mutations in the gene encoding for the cytoskeletal protein dystrophin, is an inherited disease characterized by progressive muscle weakness. Besides the relatively well characterized skeletal muscle degenerative processes, DMD is also associated with cardiac complications. These include cardiomyopathy development and cardiac arrhythmias. The current understanding of the pathomechanisms in the heart is very limited, but recent research indicates that dysfunctional ion channels in dystrophic cardiomyocytes play a role. The aim of the present study was to characterize abnormalities in L-type calcium channel function in adult dystrophic ventricular cardiomyocytes. By using the whole cell patch-clamp technique, the properties of currents through calcium channels in ventricular cardiomyocytes isolated from the hearts of normal and dystrophic adult mice were compared. Besides the commonly used dystrophin-deficient mdx mouse model for human DMD, we also used mdx-utr mice, which are both dystrophin- and utrophin-deficient. We found that calcium channel currents were significantly increased, and channel inactivation was reduced in dystrophic cardiomyocytes. Both effects enhance the calcium influx during an action potential (AP). Whereas the AP in dystrophic mouse cardiomyocytes was nearly normal, implementation of the enhanced dystrophic calcium conductance in a computer model of a human ventricular cardiomyocyte considerably prolonged the AP. Finally, the described dystrophic calcium channel abnormalities entailed alterations in the electrocardiograms of dystrophic mice. We conclude that gain of function in cardiac L-type calcium channels may disturb the electrophysiology of the dystrophic heart and thereby cause arrhythmias.

Keywords Pubmed: Action Potentials/physiology
Animals
Calcium Channels, L-Type/metabolism*
Cardiomyopathies/complications
Cardiomyopathies/metabolism
Cardiomyopathies/physiopathology
Computer Simulation
Disease Models, Animal
Heart/physiopathology*
Humans
Mice
Mice, Inbred mdx
Models, Cardiovascular
Muscular Dystrophy, Duchenne/complications
Muscular Dystrophy, Duchenne/metabolism
Muscular Dystrophy, Duchenne/physiopathology*
Myocardium/metabolism*
Myocytes, Cardiac/metabolism
Myocytes, Cardiac/physiology*


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