Effects of non-toxic doses of ouabain on sodium, potassium, calcium distribution in guinea pig papillary muscle. Electronprobe microanalysis

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Abstract
Summary The mechanisms and the cellular structures which are definitely involved in the accumulation and release of calcium in heart muscle treated with cardiac glycosides are not yet known. The distribution of sodium, potassium and calcium in small papillary muscles of the guinea pig right ventricle was examined with the aid of energy dispersive x-ray microanalysis and cryotechniques. The primary aim of the present study was twofold: firstly, to determine whether an increase in intracellular sodium concentration is detectable in muscles showing positive inotropy resulting from treatment with non-toxic doses of ouabain; and secondly, whether at the end of diastole cellular stores are detectable accumulating Ca which could be responsible for the pronounced contraction which normally would follow. Analyses on interstitium, cell membrane, sarcomeres, Z-lines and mitochondria of 7 muscles strips treated with non-toxic doses of ouabain and frozen at the end of diastole showed the following: sodium concentration in the sarcoplasm was significantly higher than over the mitochondria; it was also higher than over the sarcoplasm of non-treated muscles frozen at the end of diastole. High calcium concentrations were also measured over the cell membrane. These calcium concentrations were higher than that detected in sarcomeres, Z-lines and mitochondria. Over the sarcomeres, the calcium concentration was higher than in experiments on non-treated muscles which were also frozen at the end of diastole. Mitochondria did not accumulate any detectable concentration of calcium. The comparison of the present results with those obtained from analysis on muscles frozen after other positive inotropic interventions indicate the following cardiac glycoside-specific effects: 1) increase in intracellular sodium concentration; 2) accumulation of high calcium mass fraction during diastole in structures connected with the cell membrane — their role in activation of contraction remains to be proved — and 3) increased calcium concentration over the sarcomeres. The results strongly support the classical hypothesis that cardiac glycosides act via inhibition of the Na-K pump. Such inhibition, involving the Na/Ca exchange, would lead to an increase in cytoplasmic calcium which, in turn, is finally responsible for the positive inotropic effect. Key words Ouabain electronprobe microanalysis calcium stores intracellular sodium