AJP - Heart and Circulatory Physiology, Vol 242, Issue 1 79-H88, Copyright © 1982 by American Physiological Society
Effects of inorganic phosphate on ion exchange, energy state, and contraction in mammalian heart
J. E. Ponce-Hornos and G. A. Langer
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.
