Thyroid hormone increases pacemaker activity in rat neonatal atrial myocytes.
Thyroid hormone increases pacemaker activity in rat neonatal atrial myocytes.
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甲状腺激素增加大鼠新生心房肌细胞的起搏器活性。
DOI：
10.1006/jmcc.2001.1353
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发表时间：
2001
影响因子：
5
通讯作者：
Coetzee,WA
中科院分区：
文献类型：
--
作者：
Sun,ZQ;Ojamaa,K;Nakamura,TY;Artman,M;Klein,I;Coetzee,WA
使用从 2 日龄大鼠中培养的自发跳动的新生心房肌细胞，通过电生理学和药理学方法研究了甲状腺激素（3,3',5-三碘-L-甲状腺氨酸，T3）对起搏器活性的影响。用 T3(10−8m) 治疗 24-48 小时可产生正变时作用。 T3处理的细胞的搏动率为244±19次/分钟，而对照细胞的搏动率为122±10次/分钟(P<0.05)。记录动作电位，结果显示 T3 的主要作用是增加舒张期去极化率（T3 治疗组为 99.5±9.8，未治疗组为 44.0±7.8 mV/s）。一些表现出起搏器活性的细胞在电压钳条件下缺乏起搏器电流(If)。在12个自发活动的对照细胞中的5个和10个T3处理的细胞中的6个中记录了If。在那些表现出起搏器电流的细胞中，T3处理的细胞的If密度显着更大（对照中为-7.9±2.6 pA/pF v-1.8±0.5 pA/pF）。两组的L型Ca2+电流密度相似（治疗组为-7 mV，-7.5±1.5，对照组为-8.6±1.0 pA/pF）。在 T3 存在的情况下，Na+–Ca2+ 交换电流 (INa/Ca) 密度较大（例如，在 +60 mV 时，对照细胞中为 4.8±0.5 v 3.5±0.2 pA/pF，P<0.05）。当细胞内 Ca2+ 从细胞中挤出时，生电的 Na+–Ca2+ 交换器会导致内向电流下降，这可能有助于起搏器电位——使用动作电位电压钳技术证明了这种下降的内向电流，并且在 T3 处理的心肌细胞中显示更大。我们的数据表明，甲状腺激素可增强起搏器活性，这可能部分归因于 Na+–Ca2+ 交换器活性的增加。
The effects of thyroid hormone (3,3′,5-triiodo- L -thyronine, T3) on pacemaker activity were studied with electrophysiological and pharmacological approaches using spontaneously beating neonatal atrial myocytes cultured from 2-day-old rats. Treatment with T3(10−8m) for 24–48 h led to a positive chronotropic effect. The beating rate of T3-treated cells was 244±19 beats/min and for control cells it was 122±10 beats/min (P<0.05). Action potentials were recorded and showed that the predominant effect of T3was to increase the diastolic depolarization rate (99.5±9.8 in T3-treated group v 44.0±7.8 mV/s in untreated group). Some cells that exhibited pacemaker activity lacked a pacemaker current (If) under voltage clamp conditions Ifwas recorded in 5 of 12 spontaneously active control cells and in 6 of 10 T3-treated cells. In those cells exhibiting the pacemaker current, the Ifdensity was significantly larger in T3-treated cells (−7.9±2.6 pA/pF v−1.8±0.5 pA/pF in control). The L-type Ca2+current density was similar in the two groups (at −7 mV, −7.5±1.5 in treated groupv −8.6±1.0 pA/pF in control). In the presence of T3, the Na+–Ca2+exchanger current (INa/Ca) density was larger (e.g. at +60 mV, it was 4.8±0.5 v 3.5±0.2 pA/pF in control cells, P<0.05). As intracellular Ca2+is extruded from the cell, the electrogenic Na+–Ca2+exchanger causes a declining inward current, which may contribute to the pacemaker potential—this declining inward current was demonstrated using the action potential voltage clamp technique and was shown to be larger in T3-treated myocytes. Our data demonstrate that thyroid hormone enhances pacemaker activity and that this may be due in part to an increased Na+–Ca2+exchanger activity.