DEPRESSED TRANSIENT OUTWARD CURRENT-DENSITY IN VENTRICULAR MYOCYTES FROM CARDIOMYOPATHIC SYRIAN-HAMSTERS OF DIFFERENT AGES

We determined whether the dilated cardiomyopathy which develops betwee n 30 and 140 days of age in the Syrian hamster strain MS200, before th e onset of cardiac hypertrophy and failure, is associated with alterat ions in both the action potential (AP) and the Ca2+-independent transi ent outward current, I-to1. AP was recorded in perfused hearts using m icroelectrodes and I-to1 was recorded in single ventricular myocytes u sing the whole-cell patch-clamp. The MS200 strain was compared to the control CHF148 strain at different periods of age (60, 90, 120 and 180 days). APs were markedly lengthened in MS200 compared to CHF148 heart s at all ages studied. Cell membrane capacitance increased with age in the two strains, but was not significantly higher in MS200 than in CH F148 of a given age, indicating the absence of cell hypertrophy. At 69 days of age, I-to1 density was the same in the two strains. Later on, I-to1 density increased markedly at 90-120 days then decreased at 180 days in CHF148, whereas this increase was delayed and of reduced ampl itude in MS200. The sustained component of outward current, I-SUS, was not sizeably different in the two strains, The conductance-voltage an d steady-state inactivation relationships were shifted with age toward s positive potentials by 15 mV in the two strains, but earlier in MS20 0 (90 days) than in CHF148 (180 days). Similarly, the recovery of I-to 1 from inactivation exhibited a slow component which increased with ag e in the two strains but was larger in MS200 than in CHF148. In conclu sion, alterations of I-to1 may contribute to changes in shape of AP, b ut cannot entirely explain dilation-induced AP lengthening. (C) 1996 A cademic Press Limited