| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
A purpose of this study was to determine whether Na^+ channels play an important role in developmental changes in the positive inotropic action of ouabain in isolated rat hearts. This was a two year study conducted from 1990 through 1991.
1. Inotropic studies
(1) The positive inotropic effects of ouabain in isolate ventricular muscle preparations of prenatal (21 day gestation) and adult (4 month old) rat hearts, and the positive inotropic effects in the absence and presence of pharmacological blocking agents. : In both prenatal and adult rat hearts, ouabain caused biphasic positive inotropic effects (low dose and high dose effects). The low dose effect, however, was significantly lower in prenatal hearts. The biphasic positive inotropic effects were not altered by adrenergic or histaminergic receptor antagonists, but were signif icantly enhanced by veratridine.
(2) The inotropic effects of several neurotoxins in isolated ventricular muscles of prenatal and adult rat hearts. : In both pren
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atal and adult hearts, tetrodotoxin caused negative inotropic effects, while veratridine, anemonia sulcata toxin or androctonus australis toxin caused positive inotropic effects. Prenatal hearts required higher concentrations in all of these neurotoxins to produce comparable inotropic effects. Centruroides sculpturatus toxin caused positive inotropic effects in adult hearts, however, this toxin failed to cause the positive inotropic effects in prenatal hearts.
2. [ ^3H]ouabain binding studies
A scatchard plot analysis of the specific binding of[ ^3H]ouabain revealed high and low-af finity binding sites in both the homogenates obtained from the ventricular muscles of prenatal or adult rat heart. The ratio of the high and low affinity binding site concentrations observed in prenatal and adult rat hearts was 1 : 8 and 1 : 4, respectively.
These results suggest that cardiac Na^+ channels undergo significant functional changes during development. Since a slight elevation of intracellular Na^+ concentration, during the diastolic phase of the cardiac cycle, may be sufficient to cause the positive inotropic effects of digitalis ; the developmental increase in Na^+ channels may play an important role in the increase in the sensitivity of the heart to ouabain. In addition, developmental changes in the biochemical characteristics of Na^+, K^+-ATPase may also contribute to the increase in the ouabain sensitivity with the maturity of the rat. Less
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