IONIC BASIS OF THE ACTION-POTENTIAL PROLONGATION IN VENTRICULAR MYOCYTES FROM SYRIAN-HAMSTERS WITH DILATED CARDIOMYOPATHY

Objective: The aim of our study was to determine the main electrophysi ological alterations associated with cardiac dilation in MS200 strain Syrian hamsters, a model of genetically determined cardiomyopathy. Met hods: Ventricular action potentials (APs) were recorded with standard microelectrodes in isolated hearts from 120-day-old cardiomyopathic (s train MS200) and age-matched control (strain CHF148) Syrian hamsters, Ionic currents were recorded from single ventricular myocytes using th e whole-cell patch-clamp technique. Results: In MS200, AP was prolonge d and the plateau phase was markedly increased as compared to CHF148. Differences in both AP duration and 4-aminopyridine-induced AP lengthe ning between epicardial and endocardial tissues were less marked in MS 200 than in CHF148 ventricles. Cell size and membrane capacitance were not higher in MS200 than in CHF148 myocytes, indicating the absence o f cell hypertrophy in myopathic ventricles. The L-type calcium current (I-Ca,I-L) density was significantly reduced in MS200 and the voltage -dependence of both steady-state activation and inactivation was alter ed. The voltage-dependent outward current was composed of both transie nt (I-tol) and sustained (I-ss) components, respectively sensitive and insensitive to 4-aminopyridine. I-tol density was strongly depressed in MS200 compared to CHF148, whereas I-ss density was only slightly re duced, The conductance-voltage and steady-state inactivation relations hips for I-tol were shifted to more positive potentials in MS200. The I-tol recovery process was markedly slower in MS200 than in CHF148. Th e steady-state current-voltage relationships, in the physiological vol tage range, were superimposable in MS200 and CHF148, Conclusions: In v entricular myocytes from dilated heart of MS200 Syrian hamsters, I-tol is more drastically depressed than I-Ca,I-L. Such an observation migh t partially explain dilation-induced AP lengthening.