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 were 2, 12 and 90 min, respectively. 4. The release of ⁴⁵Ca from the slowly exchanging compartment (t½ 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.
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