Regulation of mitochondrial matrix pH and adenosine 5'-triphosphatase activity during ischemia in slow heart-rate hearts. Role of Pi/H+ symport.
During ischemia in so-called slow heart-rate hearts, there is a marked inhibition of the mitochondrial ATPase mediated by inhibitor protein binding to the enzyme (Rouslin, W., and Pullman, M. E. (1987) J. Mol. Cell. Cardiol. 19, 661-668). This ischemia-induced ATPase inhibition is triggered by a drop in mitochondrial matrix pH (Rouslin, W. (1987) J. Biol. Chem. 262, 3472-3476) which occurs as a result of the cell acidification which develops rapidly during the ischemic process. One effect of the ATPase inhibition is a marked slowing of the net rate of tissue ATP hydrolysis and, thus, a prolongation of cell viability during ischemia. In the present study, we demonstrate that matrix acidification in intact mitochondria from slow heart-rate hearts appears to be mediated by the Pi transporter. Pi/H+ symport appears to be the primary process which mediates matrix acidification and thus ATPase inhibition in intact slow heart-rate heart mitochondria made acidotic in vitro and, presumably, also in mitochondria in situ during the ischemic process. In contrast, intact mitochondria from a so-called fast heart-rate species, which exhibited only a low level of ischemia-induced ATPase inhibition in situ (Rouslin, W. (1987) Am. J. Physiol. 252, H622-H627), failed to exhibit a Pi- and pH-dependent mitochondrial ATPase inhibition mechanism in vitro. The Pi-dependent mitochondrial ATPase inhibition mechanism reported here for slow heart-rate hearts is consistent with a role for Pi as a coordinating signal promoting the conservation of cell ATP during myocardial ischemia.
Rouslin
W
W
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0575.
Broge
C W
CW
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D010856:Columbidae; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D005033:Ethylmaleimide / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D011817:Rabbits
D002352:Carrier Proteins; D010710:Phosphates; D000251:Adenosine Triphosphatases; D005033:Ethylmaleimide