Heterogeneity of action potential waveforms and potassium currents in rat ventricle

OBJECTIVE: The ionic mechanisms for differences in action potential waveforms in rat left ventricle were studied by recording L-type Ca2+ current, transient outward K+ current, and inwardly rectifying background K+ current in single myocytes. METHODS: Single cells were obtained from adult rat hearts by enzymatic dispersion of tissue segments from the epicardium at the apex and the endocardium at the base of the left ventricle. Whole cell voltage clamp methods together with cell shortening measurements were used to identify the K+ currents involved in early and late repolarisation and to correlate changes in action potential shape with inotropic responses. 4-Aminopyridine was used to block the transient outward K+ current, I(t), to evaluate the contribution of this current to repolarisation. RESULTS: Action potential recordings demonstrated 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 pronounced action potential lengthening and inotropic effects on cells from epicardium than on myocytes from endocardium suggesting that I(t) is larger in the epicardium. Voltage clamp measurements confirmed this. In contrast, the L-type Ca2+ current, the resting membrane potential, and the inwardly rectifying background K+ current were very similar in these two regions of left ventricle. CONCLUSIONS: One significant factor 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 potential duration have important implications for the gradient of repolarisation in rat left ventricle, for the genesis of the T wave of the electrocardiogram, and for both electrical and mechanical restitution (refractoriness).