EXPRESSION OF ADENINE-NUCLEOTIDE TRANSLOCATOR PARALLELS MATURATION OFRESPIRATORY CONTROL IN HEART IN-VIVO

Changes in the relationship between myocardial high-energy phosphates and oxygen consumption in vivo occur during development, implying that the mode of respiratory control undergoes maturation. We hypothesized that these maturational changes in sheep heart are paralleled by alte rations in the adenine nucleotide translocator (ANT), which are in tur n related to changes in the expression of this gene. Increases in myoc ardial oxygen consumption (M(V) over dot(O2)) were induced by epinephr ine infusion in newborn (0-32 h, n = 6) and mature sheep (30-32 days, n = 6), and high-energy phosphates were monitored with P-31 nuclear ma gnetic resonance. Western blot analyses for the ANT(1) and the beta-su bunit of F-1-adenosinetriphosphatase (ATPase) were performed in these hearts and additional (n = 9 total per group) as well as in fetal hear ts (130-132 days of gestation, n = 5). Northern blot analyses were per formed to assess for changes in steady-state RNA transcripts for these two genes. Kinetic analyses for the P-31 spectra data revealed that t he ADP-M(V) over dot(O2) relationship for the newborns conformed to a Michaelis-Menten model but that the mature data did not conform to fir st-or second-order kinetic control of respiration through ANT. Maturat ion from fetal to mature was accompanied by a 2.5-fold increase in ANT protein (by Western blot), with no detectable change in beta-F-1-ATPa se. Northern blot data show that steady-state mRNA levels for ANT and beta-F-1-ATPase increased similar to 2.5-fold from fetal to mature. Th ese data indicate that 1) respiratory control pattern in the newborn i s consistent with a kinetic type regulation through ANT, 2) maturation al decreases in control through ANT are paralleled by specific increas es in ANT content, and 3) regulation of these changes in ANT may be re lated to increases in steady-state transcript levels for its gene.