Influence of thyroid status on postnatal maturation of calcium channels, beta-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), Ca(2+)-release channels of sarcoplasmic reticulum (ryanodine receptors), beta-adrenoceptors, thapsigargin-sensitive Ca(2+)-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 ryanodinerece receptors (reduced by 23% and 31%, respectively, with respect to euthyroid controls), and much reduced levels of beta-adrenoceptors, Ca(2+)-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 alpha 2 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 beta-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.
Wibo
M
M
Laboratoire de Pharmacologie, Université Catholique de Louvain, Bruxelles, Belgium.
Kilar
F
F
Zheng
L
L
Godfraind
T
T
D000375:Aging / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis*; D020746:Calcium Channels, L-Type; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis*; D006321:Heart / Q000254:growth & development*; D006352:Heart Ventricles; D006980:Hyperthyroidism / Q000378:metabolism / Q000503:physiopathology*; D007037:Hypothyroidism / Q000378:metabolism / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis*; D012016:Reference Values; D019837:Ryanodine Receptor Calcium Release Channel; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis*; D013961:Thyroid Gland / Q000502:physiology*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D011943:Receptors, Adrenergic, beta; D019837:Ryanodine Receptor Calcium Release Channel; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase