Perpetuation of misinterpretations due to lack of methodical insight. A critical re-evaluation of the determination of 45Ca release from intact guinea-pig atria.

1. The evaluation of still more pretentious and complicated methods is accompanied by a decline of methodical knowledge outside of the own technical field. Interpretations or extrapolations are taken as granted without critical examination of the methodical steps applied. An example is given by re-evaluating the 45Ca release from isolated cardiac tissue and the possible interpretations. 2. 45Ca release and tissue Ca content were measured in isolated guinea-pig left atria during Ca equilibrium and under conditions known to induce net Ca movements. 3. At equilibrium condition (1.8 mM Na2+0) 3 exponential phase of 45Ca release from the atria were observed. The compartments contained 61%, 29% and 10% of total 45Ca; the t1/2 were 2, 12 and 90 min, respectively. 4. The release of 45Ca from the slowly exchanging compartment (t1/2 90 min) decreased during incubation in nominal Ca-free solution, although a net loss of tissue Ca occurred. Addition of EGTA (5 x 10(-5) M) to the washout medium abolished this retardation of 45Ca release. 5. At external Na+ concentrations below 40 mM (substituted by sucrose), the 45Ca release from the slowly exchanging compartment decreased. Simultaneously, the tissue Ca content increased massively. The 45Ca release was further reduced in Na-poor, nominal Ca-free solution. Under both conditions, the presence of EGTA in the washout medium normalized the rate of 45Ca release. 6. The results suggest that the apparent decline of 45Ca release from intact atria upon reduction of the external Ca and Na concentration does not reflect a decrease of the cellular efflux rate, but is the consequence of an enhanced re-uptake of 45Ca from the extracellular space into the myocardial cells. The probability for the released 45Ca either to escape into the organ bath or to become reabsorbed depends on the specific radioactivity of 45Ca in the extracellular space during the washout phase. Thus, this experimental procedure is not suited to demonstrate a Na-Ca exchange at the cardiac sarcolemma.