Scholarlink

<p>Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) cultured in the presence of retinoic acid were proposed as a model for human atrium. Since in the human heart positive inotropic effects of serotonin (5-HT) are restricted to the atrium, we investigated whether the presence of 5-HT responses may distinguish between hiPSC-atrial and ventricular CM. Nonfiltered retinoic acid (1&#xa0;µM) was used to induce an atrial phenotype (hiPSC-aCM) in two different hiPSC lines. Untreated hiPSC-CM were used as controls (ventricular). We measured 5-HT4 receptor (<i>HTR4</i>) expression and 5-HT effects on Ca<sup>2+</sup> currents (I<sub>Ca</sub>), force, and action potential in engineered heart tissue (EHT). <i>HTR4</i> transcript abundance was five times higher in atrial EHT. 5-HT (100 µM) increased I<sub>Ca</sub> from 5.3 ± 0.8 to 8.1 ± 1.1 pA/pF, prolonged APD<sub>20</sub> from 8.1 ± 1.2 to 12.0 ± 1.2 ms, and shortened APD<sub>90</sub> from 142.3 ± 11.3 to 117.0 ± 6.6 ms in hiPSC-aCM, but not in hiPSC-vCM. 5-HT increased force in atrial EHTs from 0.06 ± 0.01 to 0.10 ± 0.01 mN but not in vEHT. Spontaneous beating rate per minute was increased by 5-HT in aEHT from 151.3 ± 7.5 to 173.7 ± 4.1 and in vEHT from 43.1 ± 4.2 to. 61.3 ± 3.4. Both EHTs contain functional 5-HT receptors, but 5-HT increases I<sub>Ca</sub> and force only in aEHT, similar to the human heart. In vEHT, 5-HT’s positive chronotropic effect in the absence of I<sub>Ca</sub> stimulation and inotropic response suggests activation of funny channels. Our findings demonstrate that aEHT shares the typical atrial-selective regulation of I<sub>Ca</sub> and force by 5-HT, thus making aEHT a promising model to study 5-HT<sub>4</sub> receptors in the human heart.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Positive inotropic effects of serotonin in atrial EHT: further proof for an atrial phenotype?

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月28日

查看全文
  • Muhammed Sönmez,
  • Margaret Nandudu,
  • Paul Brunnbauer,
  • Carl Schulz,
  • Birgit Klampe,
  • Thomas Schulze,
  • Arne Hansen,
  • Thomas Eschenhagen,
  • Torsten Christ

摘要

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) cultured in the presence of retinoic acid were proposed as a model for human atrium. Since in the human heart positive inotropic effects of serotonin (5-HT) are restricted to the atrium, we investigated whether the presence of 5-HT responses may distinguish between hiPSC-atrial and ventricular CM. Nonfiltered retinoic acid (1 µM) was used to induce an atrial phenotype (hiPSC-aCM) in two different hiPSC lines. Untreated hiPSC-CM were used as controls (ventricular). We measured 5-HT4 receptor (HTR4) expression and 5-HT effects on Ca2+ currents (ICa), force, and action potential in engineered heart tissue (EHT). HTR4 transcript abundance was five times higher in atrial EHT. 5-HT (100 µM) increased ICa from 5.3 ± 0.8 to 8.1 ± 1.1 pA/pF, prolonged APD20 from 8.1 ± 1.2 to 12.0 ± 1.2 ms, and shortened APD90 from 142.3 ± 11.3 to 117.0 ± 6.6 ms in hiPSC-aCM, but not in hiPSC-vCM. 5-HT increased force in atrial EHTs from 0.06 ± 0.01 to 0.10 ± 0.01 mN but not in vEHT. Spontaneous beating rate per minute was increased by 5-HT in aEHT from 151.3 ± 7.5 to 173.7 ± 4.1 and in vEHT from 43.1 ± 4.2 to. 61.3 ± 3.4. Both EHTs contain functional 5-HT receptors, but 5-HT increases ICa and force only in aEHT, similar to the human heart. In vEHT, 5-HT’s positive chronotropic effect in the absence of ICa stimulation and inotropic response suggests activation of funny channels. Our findings demonstrate that aEHT shares the typical atrial-selective regulation of ICa and force by 5-HT, thus making aEHT a promising model to study 5-HT4 receptors in the human heart.