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 hams ters which does not develop hypertrophy during the first five months of lif e. Right and left ventricular action potentials (APs) were recorded in Lang endorff perfused isolated hearts from dilated cardiomyopathic (MS 200) and normal hamsters at 60, 120, and 180 days of age. AP characteristics differe d in the two ventricles and in different regions (base, apex) of the left v entricle in both strains. When recorded in a given region taper), the plate au was always of higher amplitude and longer duration, i.e., of larger area , in diseased as compared to normal hearts. The participation of the calciu m-independent 4-aminopyridine (4-AP) sensitive transient outward current, I -tol, in the left ventricular AP plateau repolarization was smaller in dila ted than in control hearts at any age and AP area was the same in both stra ins at 60 days of age in the presence of 4-AP. The participation of the cad mium (Cd) sensitive L-type Ca current was investigated in the development o f 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 remaine d high in diseased hearts. The tetrodotoxin sensitive slowly inactivating i nward current was not increased in dilated hearts compared to control heart s. Our results show that the AP lengthening observed, in dilated non-hypert rophic hamster hearts, results essentially from a reduced participation of I-tol at 60 days of age, whereas it results from both a reduced participati on of I-tol and an increased participation of INa-Ca at 120 and 180 days of age.