Respiratory control in the glucose perfused heart

FEBS Letters

Balaban, Robert S.¹  Katz, Lawrence A.¹  Koretsky, Alan P.¹ 

[1] National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA

关键词: ADP;    ATP;    Energy metabolism;    Pi;    Creatine phosphate;    Mitochondria;    (Rat heart);   

DOI  :  10.1016/0014-5793(87)80939-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The phosphate metabolises, adenosine diphosphate (ADP), inorganic phosphate (P_i), and adenosine triphosphate (ATP), are potentially important regulators of mitochondrial respiration in vivo. However, previous studies on the heart in vivo and in vitro have not consistently demonstrated an appropriate correlation between the concentration of these phosphate metabolites and moderate changes in work and respiration. Recently, mitochondrial NAD(P)H levels have been proposed as a potential regulator of cardiac respiration during alterations in work output. In order to understand better the mechanism of respiratory control under these conditions, we investigated the relationship between the phosphate metabolites, the NAD(P)H levels, and oxygen consumption (Q₀₂) in the isovolumic perfused rat heart during alterations in work output with pacing. ATP, creatine phosphate (CrP), P_i and intracellular pH were measured using ³¹P NMR. Mitochondrial NAD(P)H levels were monitored using spectrofluorometric techniques. Utilizing glucose as the sole substrate, an increase in paced heart rate led to an increase in Q₀₂ from 1.73 ± 0.09 to 2.29 ± 0.12 mmol Q₂/h per g dry wt. No significant changes in the levels of P_i, PCr, ATP, or the calculated ADP levels were detected. Under identical conditions, an increase in heart rate was associated with a 23±3% increase in NAD(P)H fluorescence. Thus, under the conditions of these studies, an increase in Q₀₂ was not associated with an increase in ADP or P_i. In contrast, increases in Q₀₂ were associated with an increase in NAD(P)H. These data are consistent with the notion that increases in the mitochondrial NADH redox state regulate steady-state levels of respiration when myocardial work is increased.

【 授权许可】

Unknown