Dilation and action potential lengthening in cardiomyopathic Syrian hamster heart.
The aim of our study was to determine the main ionic mechanisms responsible for the electrophysiological alterations of ventricular action potentials associated with cardiac dilation in a strain of cardiomyopathic Syrian hamsters which does not develop hypertrophy during the first five months of life. Right and left ventricular action potentials (APs) were recorded in Langendorff perfused isolated hearts from dilated cardiomyopathic (MS 200) and normal hamsters at 60, 120, and 180 days of age. AP characteristics differed in the two ventricles and in different regions (base, apex) of the left ventricle in both strains. When recorded in a given region (apex), the plateau was always of higher amplitude and longer duration, i.e., of larger area, in diseased as compared to normal hearts. The participation of the calcium-independent 4-aminopyridine (4-AP) sensitive transient outward current, Ito1, in the left ventricular AP plateau repolarization was smaller in dilated than in control hearts at any age and AP area was the same in both strains at 60 days of age in the presence of 4-AP. The participation of the cadmium (Cd) sensitive L-type Ca current was investigated in the development of AP plateau at 120 days of age and was smaller in dilated than in control hearts. The participation of the Na-Ca exchange inward current, INa-Ca, in the development of the AP plateau was similar in both strains at 60 days of age; later on, it strongly decreased in control hearts, whereas it remained high in diseased hearts. The tetrodotoxin sensitive slowly inactivating inward current was not increased in dilated hearts compared to control hearts. Our results show that the AP lengthening observed, in dilated non-hypertrophic hamster hearts, results essentially from a reduced participation of Ito1 at 60 days of age, whereas it results from both a reduced participation of Ito1 and an increased participation of INa-Ca at 120 and 180 days of age.
Deroubaix
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E
Laboratoire de Cardiologie Moléculaire et Cellulaire, CNRS ESA 8078, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
Thuringer
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D
Coulombe
A
A
Mercadier
J J
JJ
Coraboeuf
E
E
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D006332:Cardiomegaly / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D006224:Cricetinae; D008647:Mesocricetus; D015222:Sodium Channels / Q000502:physiology; D016276:Ventricular Function
D015220:Calcium Channels; D015222:Sodium Channels; D015761:4-Aminopyridine