Wibo M, Kilar F, Zheng L, Godfraind T
Laboratoire de Pharmacologie, Université Catholique de Louvain, Bruxelles, Belgium.
J Mol Cell Cardiol. 1995 Aug;27(8):1731-43. doi: 10.1016/s0022-2828(95)90887-0.
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.
为了研究甲状腺激素对出生后心脏兴奋 - 收缩偶联发育的影响，将新生大鼠制成甲状腺功能减退或亢进模型，并对直接或间接参与Ca2+信号传导的几个关键因素进行了研究：L型Ca2+通道（1,4 - 二氢吡啶受体）、肌浆网Ca(2+)释放通道（兰尼碱受体）、β - 肾上腺素能受体、毒胡萝卜素敏感的Ca(2+) - ATP酶和Na(+) - K(+) - ATP酶（酶活性和哇巴因受体），这些研究是在第21天收集的心室组织膜组分中进行的。甲状腺功能减退导致1,4 - 二氢吡啶和兰尼碱受体的心肌密度适度降低（相对于甲状腺功能正常的对照组分别降低23%和31%），并且β - 肾上腺素能受体、Ca(2+) - ATP酶和Na(+) - K(+) - ATP酶活性水平大幅降低。甲状腺功能亢进仅导致1,4 - 二氢吡啶受体的心肌密度适度降低（22%）以及Na(+) - K(+) - ATP酶α2亚型显著增加（240%）。为了分析L型通道的肌膜下定位，通过在蔗糖梯度中进行密度平衡对微粒体组分进行亚分级分离。在来自对照和甲状腺功能亢进大鼠的梯度中，大多数1,4 - 二氢吡啶受体在高密度亚组分中回收，其分布与兰尼碱受体一致，而在来自甲状腺功能减退大鼠的梯度中，大多数1,4 - 二氢吡啶受体在低密度亚组分中回收，与β - 肾上腺素能受体和Na(+) - K(+) - ATP酶一起。我们得出结论，甲状腺激素对于参与Ca2+通量的几种通道和泵的心肌密度的出生后变化很重要，并且对于L型Ca2+通道从非连接肌膜到连接结构的出生后重新分布也很重要，这是成年心室组织中兴奋 - 收缩偶联有效运作的关键过程。
