Evidence that concentrations of ouabain which induce positive inotropic effects on the perfused guinea-pig heart increase the amount of calcium in a rapidly-exchangeable cellular compartment

The effects of ouabain and adrenaline on kinetically distinct compartments of exchangeable calcium associated with myocardial muscle cells were investigated using a Langendorff perfused guinea-pig heart preparation, a ⁴⁵Ca²⁺ outflow exchange technique, and ⁵¹Cr-EDTA to monitor the rate of loss of freely-diffusable ⁴⁵Ca²⁺ from the vascular and interstitial spaces. A non-linear least squares curve-fitting procedure was used to analyse the data. The minimum number of compartments of exchangeable calcium required to adequately describe each set of data for the loss of ⁴⁵Ca from the heart was five. These consisted of freely-diffusible exchangeable calcium in the vascular and interstitial spaces (monitored using ⁵¹Cr-EDTA) and three kinetically distinct compartments of exchangeable calcium associated with the muscle cells. A concentration of ouabain (0.15 μM), which enhanced the force of contraction of the heart by 60% without evidence of toxicity, increased the flux and quantity of exchangeable calcium in the vascular space and in the cellular compartment with the highest fractional transfer rate. Both ouabain and adrenaline decreased the flux and fractional transfer rate of exchangeable calcium in the two cellular compartments with the lowest fractional transfer rates. The results are consistent with the conclusion that one of the actions of ouabain on myocardial muscle cells is to increase the quantity of rapidly-exchangeable calcium bound to extracellular sites on the sarcolemma and/or present in the myoplasm.