Maturation in liver mitochondria of Ruthenium Red-sensitive calcium-ion-transport activity and the influence of glucagon administration in vivo and in utero

摘要

pThe maturation of Casup2+/sup transport in mitochondria isolated from rat liver was examined, from 5 days before birth. The mitochondria used were isolated from liver homogenates by centrifugation at 22000ig/i-min. Casup2+/sup transport by mitochondria isolated from foetal liver is energy-dependent and Ruthenium Red-sensitive. The transmembrane pH gradient in these mitochondria is higher by about 7mV and the membrane potential lower by about 20mV than in adult mitochondria. The inclusion of 2mm-Psubi/sub in the incubation medium enhances the protonmotive force by approx. 30mV. The rate of Casup2+/sup influx in foetal mitochondria measured in buffered KCl plus succinate is low until about 2–3h after birth, when it increases to about 60% of adult values; approx. 24h later it has reached near-adult values. Higher rates of Casup2+/sup influx are observed in the presence of 2mm-Psubi/sub; 3–5 days before birth the rates are about one-third of adult values and decline slightly as birth approaches. By 2–3h ipost partum/i they have reached adult values. The inclusion of 12.5μm-MgATP with the Psubi/sub stimulates further the initial rate of Casup2+/sup influx in foetal mitochondria. The rates observed are constant over the prenatal period examined and are 50–60% of those observed in adult mitochondria. Mitochondria isolated from foetal livers 4–5 days before birth retain the accumulated Casup2+/sup for about 50min in the presence of 2mm-Psubi/sub. In the period 2 days before birth to birth, this ability is largely lost, but by 2–3h after birth Casup2+/sup retention is similar to that of adult mitochondria. The presence of 12.5μm-MgATP progressively enhances the Casup2+/sup retention time as development proceeds until 2–3h after birth, when it becomes less sensitive to added MgATP. Glucagon administration to older foetuses iin utero/i enhances both the rate of mitochondrial Casup2+/sup influx assayed in the presence of 2mm-Psubi/sub and the time for which mitochondria retain accumulated Casup2+/sup in the presence of 12.5μm-MgATP and 2mm-Psubi/sub. Its administration to neonatal animals leads to an increase in mitochondrial Casup2+/sup retention similar to that seen in adult mitochondria. The data provide evidence that the Ruthenium Red-sensitive Casup2+/sup transporter is potentially as active in foetal mitochondria 5 days before birth as it is in adult mitochondria. They also show that foetal mitochondria have an ability to retain accumulated Casup2+/sup reminiscent of mitochondria from tumour cells and from hormone-challenged rat liver./p