title: Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes.
abstract: OBJECTIVE
  Dysferlin plays a decisive role in calcium-dependent membrane repair in myocytes. Mutations in the encoding DYSF gene cause a number of myopathies, e.g. limb-girdle muscular dystrophy type 2B (LGMD2B). Besides skeletal muscle degenerative processes, dysferlin deficiency is also associated with cardiac complications. Thus, both LGMD2B patients and dysferlin-deficient mice develop a dilated cardiomyopathy. We and others have recently reported that dystrophin-deficient ventricular cardiomyocytes from mouse models of Duchenne muscular dystrophy show significant abnormalities in voltage-dependent ion channels, which may contribute to the pathophysiology in dystrophic cardiomyopathy. The aim of the present study was to investigate if dysferlin, like dystrophin, is a regulator of cardiac ion channels.
  
  
  RESULTS
  By using the whole cell patch-clamp technique, we compared the properties of voltage-dependent calcium and sodium channels, as well as action potentials in ventricular cardiomyocytes isolated from the hearts of normal and dysferlin-deficient (dysf) mice. In contrast to dystrophin deficiency, the lack of dysferlin did not impair the ion channel properties and left action potential parameters unaltered. In connection with normal ECGs in dysf mice these results suggest that dysferlin deficiency does not perturb cardiac electrophysiology.
  
  
  CONCLUSIONS
  Our study demonstrates that dysferlin does not regulate cardiac voltage-dependent ion channels, and implies that abnormalities in cardiac ion channels are not a universal characteristic of all muscular dystrophy types.
authors.affiliation: Center for Physiology and Pharmacology, Department of Neurophysiology and -Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Lena
authors.initials: L
authors.lastname: Rubi
authors.forename: Vaibhavkumar S
authors.initials: VS
authors.lastname: Gawali
authors.forename: Helmut
authors.initials: H
authors.lastname: Kubista
authors.forename: Hannes
authors.initials: H
authors.lastname: Todt
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Hilber
authors.forename: Xaver
authors.initials: X
authors.lastname: Koenig
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002413:Cations, Divalent; D002414:Cations, Monovalent; D000073939:Dysferlin; D005260:Female; D015870:Gene Expression; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D017136:Ion Transport; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D061251:Primary Cell Culture; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D002413:Cations, Divalent; D002414:Cations, Monovalent; C497505:Dysf protein, mouse; D000073939:Dysferlin; D008565:Membrane Proteins; D015222:Sodium Channels; D001464:Barium; D012964:Sodium; D002118:Calcium