Influence of thyroid status on postnatal maturation of calcium channels, β-adrenoceptors and cation transport ATPases in rat ventricular tissue

In order to examine the influence of thyroid hormones on the postnatal development of cardiac excitation-contraction coupling, newborn rats were made hypo- or hyperthyroid, and several key factors involved, directly or indirectly, in Ca2+ signaling: l-type Ca2+ channels (1,4-dihydropyridine receptors), Ca2+-release channels of sarcoplasmic reticulum (ryanodine receptors), β-adrenoceptors, thapsigargin-sensitive Ca2+-ATPase and Na+-K+-ATPase (enzyme activity and ouabain receptors), were investigated in membrane fractions from ventricular tissue, collected on day 21. Hypothyroidism induced a moderately lower myocardial density of 1,4-dihydropyridine and ryanodine receptors (reduced by 23% and 31%, respectively, with respect to euthyroid controls), and much reduced levels of β-adrenoceptors, Ca2+-ATPase and Na+-K+-ATPase activities. Hyperthyroidism induced only a moderate (22%) decrease in the myocardial density of 1,4-dihydropyridine receptors and a marked (240%) increase of the α2 isoform of Na+-K+-ATPase. To analyse the subsarcolemmal localization of l-type channels, microsomal fractions were subfractionated by density equilibration in sucrose gradient. In gradients from control and hyperthyroid rats, most 1,4-dihydropyridine receptors were recovered in high-density subfractions, their distribution following that of ryanodine receptors, whereas, in gradients from hypothyroid rats, most 1,4-dihydropyridine receptors were recovered in low-density subfractions, together with β-adrenoceptors and Na+-K+-ATPase. We conclude that thyroid hormones are important for the postnatal changes in the myocardial density of several channels and pumps involved in Ca2+ fluxes, as well as for the postnatal redistribution of l-type Ca2+ channels from non-junctional sarcolemma to junctional structures, a key process for the efficient operation of excitation-contraction coupling in adult ventricular tissue.