Effects of inorganic phosphate on ion exchange, energy state, and contraction in mammalian heart.
Effects of inorganic phosphate (Pi) on contractile function, ionic exchange, and cellular energetic state were investigated in isolated, arterially perfused, interventricular rabbit septa. The addition of 10 or 20 mM Pi to a N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffered perfusate showed 1) a decrease in developed tension due to a decrease in free Ca concentration; 2) an increase in diastolic tension; 3) a decrease in 42K uptake at the same time that 42K efflux was depressed; 4) an increase of 24Na activity; 5) an increase in tissue 47Ca activity; and 6) a decrease in tissue adenosine 5'-triphosphate (ATP) levels. If a 10-mM Pi intervention was applied without changing the free Ca concentration of the perfusate, the mechanical record showed a transient positive inotropic effect without changes in K efflux. These results are consistent with Pi-induced stimulated mitochondrial Ca uptake and Na-K pump inhibition that combine to increase cellular Ca uptake. The increase in cellular Ca and the decrease in cellular ATP would both tend to increase diastolic tension. In the presence of antimycin A, respiration-dependent Ca uptake is inhibited, and mitochondrial Ca uptake is then maintained at the expense of cellular ATP. This process of mitochondrial Ca uptake could account for the deficiency of ATP and the rigor type contracture that occurs with antimycin A. This energy-deficient state is modified if mitochondrial ATP consumption is blocked by oligomycin, and such treatment prevents the ATP-deficient rigor. Under these conditions, although mitochondrial Ca uptake is blocked by the presence of antimycin A and oligomycin, Ca uptake remains augmented secondary to Na-K pump inhibition by Pi.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
D010710:Phosphates; D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium