Membrane Abnormalities and Changes in Cardiac Cations due to Alterations in Thyroid Status

Abstract

Thyroid hormones have been shown to induce marked changes in the cardiovascular system (1–4); however, the mechanism of cardiac alterations due to changes in thyroid status over a prolonged period are poorly understood. Since sarcolemmal Na⁺-K⁺ ATPase is known to serve as a pump for maintenance of the intracellular concentrations of Na⁺ and K⁺ in the myocardial cell (5–7), changes in the activity of this enzyme can be seen to alter the cation composition of the myocardium and thus may lead to changes in the contractile activity. Previous studies have revealed that changes in the plasma levels of thyroid hormones exert a dramatic effect on the myocardial Na⁺-K⁺ ATPase activity (8–11). While some investigators have attempted to correlate thyroid hormone induced changes in cardiac Na⁺-K⁺ ATPase with alterations in the Na⁺ and K⁺ contents (9,12,13), the results are conflicting. Furthermore, very little information concerning changes in myocardial Ca²⁺ and Mg²⁺ or plasma electrolytes due to alterations in thyroid status of the animal is available in the literature. This study was therefore undertaken to investigate serum and cardiac electrolytes in euthyroid, hyperthyroid and hypothyroid animals. Experiments were also carried out to examine if the electrolyte changes due to hypothyroidism were reversible upon injecting the animals with thyroid hormone. The sarcolemmal Na⁺-K⁺ ATPase activity in euthyroid, hyperthyroid and hypothyroid hearts was monitored to seek relationship with changes in cardiac cation contents under these conditions. Furthermore, in view of varying degree of alterations in the Ca²⁺-transport activities of the cardiac sarcoplasmic reticulum from hypothyroid and hyperthyroid animals (14–18), it was considered worthwhile to study changes in the sarcoplasmic reticular function by employing heart homogenates from the control and experimental animals. It should be pointed out that these experiments with heart homogenate will not only rule out the possibility of artifacts due to the procedure for isolation of the sarcoplasmic reticulum but will also help in identifying the specificity of membrane changes upon altering the thyroid status in animals.