Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea.
College of Pharmacy.
J Clin Invest. 2020 Jul 1;130(7):3671-3683. doi: 10.1172/JCI133798.
The baroreceptor reflex is a powerful neural feedback that regulates arterial pressure (AP). Mechanosensitive channels transduce pulsatile AP to electrical signals in baroreceptors. Here we show that tentonin 3 (TTN3/TMEM150C), a cation channel activated by mechanical strokes, is essential for detecting AP changes in the aortic arch. TTN3 was expressed in nerve terminals in the aortic arch and nodose ganglion (NG) neurons. Genetic ablation of Ttn3 induced ambient hypertension, tachycardia, AP fluctuations, and impaired baroreflex sensitivity. Chemogenetic silencing or activation of Ttn3+ neurons in the NG resulted in an increase in AP and heart rate, or vice versa. More important, overexpression of Ttn3 in the NG of Ttn3-/- mice reversed the cardiovascular changes observed in Ttn3-/- mice. We conclude that TTN3 is a molecular component contributing to the sensing of dynamic AP changes in baroreceptors.
压力感受器反射是一种强大的神经反馈，调节动脉血压（AP）。机械敏感通道将脉动 AP 转换为压力感受器中的电信号。在这里，我们表明，机械敲击激活的阳离子通道蛋白 tenitin 3（TTN3/TMEM150C）对于检测主动脉弓中的 AP 变化至关重要。TTN3 在主动脉弓和结状神经节（NG）神经元的神经末梢表达。Ttn3 的基因缺失导致环境高血压、心动过速、AP 波动和压力反射敏感性受损。化学遗传沉默或激活 NG 中的 Ttn3+神经元会导致 AP 和心率增加，反之亦然。更重要的是，在 Ttn3-/- 小鼠的 NG 中过表达 Ttn3 可逆转在 Ttn3-/- 小鼠中观察到的心血管变化。我们的结论是，TTN3 是一种分子成分，有助于压力感受器对动态 AP 变化的感知。
