Effect of verapamil on phosphate-induced changes in oxidative phosphorylation and atractyloside-sensitive adenine nucleotide translocase activity in two populations of rat heart mitochondria.
Phosphate (Pi)-induced depression in cardiac mitochondrial function was studied using mitochondria isolated by two different procedures which purportedly yield two distinct populations. Subsarcolemmal mitochondria (SLM) exhibited an enhanced sensitivity to 20 mM Pi with respect to oxidative phosphorylation. Thus, a significant depression in oxidative phosphorylation in this population was seen following only 1-min treatment, whereas interfibrillar mitochondria (IFM) were unaffected. Both populations showed a similar response to 5-min treatment with Pi. The Pi-induced depression in respiration was partially, although significantly, reversed by a 50 microM concentration of the calcium antagonist verapamil, an observation which suggests a contribution of calcium to the Pi-induced defect in respiration. Pi also produced a potent inhibition of ADP uptake in both mitochondrial populations, which was in close agreement to Pi-induced modification of low amplitude shrinkage-swelling responses following ADP addition. Both of these parameters were unaffected by verapamil. Our results show an enhanced sensitivity of SLM to a verapamil-sensitive Pi-induced depression in oxidative phosphorylation. However, the potent, verapamil-insensitive decrease in adenine nucleotide translocase activity by Pi demonstrates that calcium is likely only partially involved in Pi-induced depression in oxidative phosphorylation and that a further partial contribution arises from a decrease in adenine nucleotide translocase activity.
Duan
J M
JM
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Karmazyn
M
M
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001278:Atractyloside / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D006352:Heart Ventricles / Q000201:enzymology; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009713:Nucleotidyltransferases / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010710:Phosphates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology*
D006027:Glycosides; D010710:Phosphates; D001278:Atractyloside; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D014700:Verapamil; D009713:Nucleotidyltransferases