Volume 10 Supplement 1

16th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access

Altered sodium channel function in dystrophin/utrophin-deficient cardiomyocytes

  • Xaver Koenig1,
  • Agnes Mike1,
  • Markus Mille1,
  • René Cervenka1,
  • Péter Lukács1,
  • Katrin Nagl1,
  • Xuan Bach Dang1,
  • Hannes Todt1,
  • Reginald E Bittner2 and
  • Karlheinz Hilber1Email author
BMC Pharmacology201010(Suppl 1):A25

https://doi.org/10.1186/1471-2210-10-S1-A25

Published: 16 November 2010

Background

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is an inherited disease characterized by progressive muscle weakness and degeneration. Besides the relatively well-described skeletal muscle degenerative processes, DMD and some other muscular dystrophy types are also associated with cardiovascular complications including cardiomyopathy and cardiac arrhythmias. The current understanding of the patho-mechanisms underlying these cardiovascular complications is still very limited, but recent research points to a contribution of dysfunctional ion channels in dystrophic cardiomyocytes.

Materials and methods

By using the whole cell patch-clamp technique, the functional properties of voltage-gated sodium channels were studied in cardiomyocytes derived from normal and dystrophic mice. In addition, a computer model was used to simulate the effects of altered sodium channel properties on the cardiac action potential. Besides the most common mouse model for human DMD, the dystrophin-deficient mdx mouse, we also used mice additionally carrying a mutation in the utrophin gene. The mdx-utr double mutant mouse exhibits a more severe cardiac disease phenotype than the mdx mouse, and is thought to represent a more suitable animal model for human DMD.

Results

We found that dystrophic cardiomyocytes show a reduced sodium current density compared to wild-type cardiomyocytes. In addition, extra utrophin deficiency significantly shifted both the sodium channel activation and inactivation curve to more depolarised potentials, which was not observed in only dystrophin-deficient mdx cardiomyocytes. Computer modelling revealed that the described sodium channel impairments in dystrophic cardiomyocytes suffice to affect the action potential.

Conclusions

Sodium channel dysfunction may perturb electrical impulse propagation in the dystrophic heart, and thus contribute to cardiac complications associated with the muscular dystrophies.

Declarations

Acknowledgements

Supported by the Austrian Science Fund (FWF, P19352-B11 and P21006-B11).

Authors’ Affiliations

(1)
Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna
(2)
Neuromuscular Research Department, Center for Anatomy and Cell Biology, Medical University of Vienna

Copyright

© Hilber et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.

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