Metabolic consequences of increasing intracellular calcium and force production in perfused ferret hearts.

31P nuclear magnetic resonance was used to measure the relative concentrations of phosphorus-containing metabolites in Langendorff-perfused ferret hearts. Intracellular concentrations of inorganic phosphate ([Pi]i), phosphocreatine [( PCr]i), ATP ([ATP]i) and [H+] (pHi) were determined. Exposure of the heart to strophanthidin (10-40 microM) produced an increase in developed pressure over 5-10 min. In the presence of strophanthidin, [ATP]i was unchanged, [PCr]i showed a small fall, [Pi]i showed a small rise and there was a small acidosis. Exposure of the heart to a solution in which all the Na had been replaced by K (0 Na(K) solution) produced an increase of resting pressure which then decayed. During this contracture [PCr]i fell transiently and [Pi]i rose transiently with approximately the same time course as the contracture. However, [ATP]i remained constant throughout. The exposure to the 0 Na(K) solution also produced an intracellular acidosis. The changes in [PCr]i and [Pi]i and the intracellular acidosis were all increased during perfusion with 0 Na(K) if the heart had previously been exposed to strophanthidin. The efflux of lactate from the heart was increased during the exposure to the 0 Na(K) solution. The magnitude of this increase was enhanced by prior exposure to strophanthidin. The increase of intracellular lactate (calculated from this efflux) was sufficient to account for the observed intracellular acidification. An increase of lactate efflux could also be measured when an isolated papillary muscle was exposed to the 0 Na(K) solution. The intracellular acidification produced by Na removal was substantially decreased after prevention of glycolysis either by substrate depletion or by the application of iodoacetate. Elevation of the extracellular calcium concentration ([Ca2+]o) produced a large increase of developed pressure which was accompanied by a small transient increase of [Pi]i, a decrease of [PCr]i and a small intracellular acidosis. There was also an increase of lactate efflux. After exposure to strophanthidin the same increase of [Ca2+]o decreased developed pressure. The associated rise in [Pi]i and fall in [PCr]i were increased but there was no significant acidosis under these conditions. In addition to other explanations (Allen, Eisner, Pirolo & Smith, 1985a), it is likely that the fall of force is partly accounted for by the rise of [Pi]i.