Mechanisms of developmental increase in the sensitivity to ouabain

In the present study we examined (1) the arrhythmogenic toxicity of ouabain (5 micrograms/kg/min intravenously) in anesthetized guinea pigs of 1-5 days and 3 months of age, and (2) the state of Na+-Ca2+ in the sarcolemmal vesicles isolated from these age groups. Guinea pigs of 1-5 days old tolerated 75% more ouabain than the young adults without significant alteration in the maximal inotropic response. Sodium-dependent 45Ca2+ uptake was substantially lower in the vesicles isolated from hearts of 3-day-old animals, which was characterized by a lower rate of 45Ca2+ uptake (60% Vmax), as compared to the young adults. There was no significant difference in the affinity for 45Ca2+ (Km). The apparent rate of Na+-dependent 45Ca2+ efflux was also lower in the vesicles from 3-day-old guinea pigs. However, the percent extrusion of 45Ca2+ appeared to be unchanged.