Multiple regional differences in cellular properties that regulate repolarization and contraction in the right atrium of adult and newborn dogs.

Abstract

Recent studies of isolated cardiac myocytes have generated the need for detailed information about regional electrophysiological differences in the atrium. We measured the spatial distribution of action potentials in adult and newborn canine right atria. Multiple regional differences in action potential shape and duration were found. The multiple regional differences produced an overall simple pattern: the longest action potentials occurred in the area of the sinus node, and the action potential duration decreased with increasing distance from the sinus node area. To account for the overall pattern, we tested factors considered important in causing atrial action potential shape differences (e.g., electronic interactions). None of the factors tested accounted for the regional differences. We then found regional differences in the responses to pauses, which suggested that differences in the properties of individual cells accounted for the regional repolarization differences. If so, genetic regulation of the regional differences may produce the overall pattern on a developmental basis. Experiments in newborn atria showed that only in the upper crista was the spatial pattern similar to that of the adult; there was little variability in action potential shape and duration in the other areas. As a further test for associated regional differences in cell properties, we examined for differences in the isoform expression of troponin T (TnT1, TnT2, TnT3, and TnT4), a protein important in excitation-contraction coupling. In adults, the greatest proportion of TnT1 occurred in the area of the sinus node, and its proportion decreased with increasing distance from the sinus node area in association with a relative increase in the proportion of TnT2. In newborn atria the relative amount of TnT1 was greatest in the upper crista (similar to adult), but little difference was found in the distribution of the isoforms in the other regions. The correspondence between the regional differences in repolarization and in the expression of the troponin T isoforms in adult and newborn atria suggests that 1) cellular ionic mechanisms vary regionally to coordinate differences in action potential configuration with differences in cell properties that regulate contractility and 2) genetic expression of the systems that regulate repolarization and mechanical cellular properties are under similar developmental and regional control.