HETEROGENEITY OF ACTION-POTENTIAL WAVE-FORMS AND POTASSIUM CURRENTS IN RAT VENTRICLE

Objective: The ionic mechanisms for differences in action potential wa veforms in rat left ventricle were studied by recording L-type Ca2+ cu rrent, transient outward K+ current, and inwardly rectifying backgroun d K+ current in single myocytes. Methods: Single cells were obtained f rom adult rat hearts by enzymatic dispersion of tissue segments from t he epicardium at the apex and the endocardium at the base of the left ventricle. Whole cell voltage clamp methods together with cell shorten ing measurements were used to identify the K+ currents involved in ear ly and late repolarisation and to correlate changes in action potentia l shape with inotropic responses. 4-Aminopyridine was used to block th e transient outward K+ current, I(t), to evaluate the contribution of this current to repolarisation. Results: Action potential recordings d emonstrated that cells from endocardial tissue at the base of the left ventricle have a considerably longer action potential than those from epicardial tissue at the apex. 4-Aminopyridine had a much more pronou nced action potential lengthening and inotropic effects on cells from epicardium than on myocytes from endocardium suggesting that I(t) is l arger in the epicardium. Voltage clamp measurements confirmed this. In contrast, the L-type Ca2+ cur-rent, the resting membrane potential, a nd the inwardly rectifying background K+ current were very similar in these two regions of left ventricle. Conclusions: One significant fact or contributing to the heterogeneity of action potential waveforms in rat left ventricle is a differential distribution of a Ca+ independent transient outward K+ current, I(t). Regional differences in action po tential duration have important implications for the gradient of repol arisation in rat left ventricle, for the genesis of the T wave of the electrocardiogram, and for both electrical and mechanical restitution (refractoriness).