Beekman R E, van Hardeveld C, Simonides W S
Laboratory for Physiology, Free University, Amsterdam, The Netherlands.
Biochim Biophys Acta. 1988 Apr 2;969(1):18-27. doi: 10.1016/0167-4889(88)90083-3.
The effects of the thyroid state on the cytosolic free Ca2+ concentration, [Ca2+]i, of resting and K+-depolarized cardiomyocytes were studied using the fluorescent Ca2+ indicator fura2. The mean resting [Ca2+]i in euthyroid myocytes (89 +/- 8 nM) was not significantly different from that in hyperthyroid myocytes (100 +/- 14 nM). The resting O2-consumption rate was identical for both groups when expressed per mg protein, but a 35% higher value was observed in the hyperthyroid group when expressed per cell on account of the cellular hypertrophy induced by thyroid hormone. Potassium induced depolarization (50 mM [K+]0) raised the level of [Ca2+]i by 50% in both groups. When ATP-coupled respiration was blocked with oligomycin, the 50 mM K+-induced rise in [Ca2+]i was accompanied in both groups by a 40% rise in glycolytic activity as inferred from measurement of lactate production. Ca2+-fluorescence transients were recorded from electrically stimulated myocytes of euthyroid, hyperthyroid and hypothyroid rats. The time taken to reach peak fluorescence (TPL) and that to 50% decay of peak fluorescence (RL0.5) decreased in the direction hypothyroid----hyperthyroid, indicating an increase in Ca2+ fluxes in the same direction. Isoproterenol (1 microM) enhanced the peak Ca2+ fluorescence in electrically stimulated hypothyroid and euthyroid myocytes but not in hyperthyroid myocytes. Both the TPL and RL0.5 were decreased by isoproterenol in euthyroid, but more so in hypothyroid myocytes. None of these parameters were influenced by isoproterenol in the hyperthyroid group. We conclude that (1) thyroid hormone increases neither the O2-consumption rate nor the level of [Ca2+]i of resting cardiomyocytes and (2) the effects of the beta-receptor-agonist isoproterenol on Ca2+ transients of electrically stimulated myocytes, are inversely related to the documented changes in beta-receptor density in heart tissue occurring with alterations in the thyroid state.
使用荧光钙指示剂fura2研究了甲状腺状态对静息和K⁺去极化心肌细胞胞质游离钙浓度（[Ca²⁺]i）的影响。甲状腺功能正常的心肌细胞的平均静息[Ca²⁺]i（89±8 nM）与甲状腺功能亢进的心肌细胞（100±14 nM）无显著差异。当以每毫克蛋白质表示时，两组的静息耗氧率相同，但由于甲状腺激素诱导的细胞肥大，当以每个细胞表示时，甲状腺功能亢进组的值高35%。钾诱导的去极化（50 mM [K⁺]₀）使两组的[Ca²⁺]i水平均升高50%。当用寡霉素阻断ATP偶联呼吸时，两组中50 mM K⁺诱导的[Ca²⁺]i升高均伴随着糖酵解活性升高40%（从乳酸产生量的测量推断）。从甲状腺功能正常、甲状腺功能亢进和甲状腺功能减退大鼠的电刺激心肌细胞记录钙荧光瞬变。达到荧光峰值的时间（TPL）和荧光峰值衰减至50%的时间（RL₀.₅）在甲状腺功能减退→甲状腺功能亢进的方向上缩短，表明钙通量在相同方向上增加。异丙肾上腺素（1 μM）增强了电刺激的甲状腺功能减退和甲状腺功能正常的心肌细胞中的钙荧光峰值，但在甲状腺功能亢进的心肌细胞中未增强。在甲状腺功能正常的心肌细胞中，异丙肾上腺素使TPL和RL₀.₅均降低，但在甲状腺功能减退的心肌细胞中降低更明显。甲状腺功能亢进组中这些参数均不受异丙肾上腺素影响。我们得出结论：（1）甲状腺激素既不增加静息心肌细胞的耗氧率也不增加[Ca²⁺]i水平；（2）β受体激动剂异丙肾上腺素对电刺激心肌细胞钙瞬变的影响与心脏组织中β受体密度随甲状腺状态改变而发生的记录变化呈负相关。
