Tentonin 3/TMEM150C senses blood pressure changes in the aortic arch
Huan-Jun Lu, Thien-Luan Nguyen, Gyu-Sang Hong, Sungmin Pak, Hyesu Kim, Hyungsup Kim, Dong-Yoon Kim, Sung-Yon Kim, Yiming Shen, Pan Dong Ryu, Mi-Ock Lee, Uhtaek Oh
Huan-Jun Lu, Thien-Luan Nguyen, Gyu-Sang Hong, Sungmin Pak, Hyesu Kim, Hyungsup Kim, Dong-Yoon Kim, Sung-Yon Kim, Yiming Shen, Pan Dong Ryu, Mi-Ock Lee, Uhtaek Oh
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Research Article Neuroscience Vascular biology

Tentonin 3/TMEM150C senses blood pressure changes in the aortic arch

Abstract

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.

Authors

Huan-Jun Lu, Thien-Luan Nguyen, Gyu-Sang Hong, Sungmin Pak, Hyesu Kim, Hyungsup Kim, Dong-Yoon Kim, Sung-Yon Kim, Yiming Shen, Pan Dong Ryu, Mi-Ock Lee, Uhtaek Oh

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Figure 3

TTN3 is required for pressure-evoked action potentials in the ADN.

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TTN3 is required for pressure-evoked action potentials in the ADN. (A) S...
(A) Schematic illustration of ex vivo recording from an isolated ADN attached to the aortic arch. (B) Representative traces of multiunit activities in response to intra-aortic pressures in WT and Ttn3–/– mice. Aortic pressure is shown in the middle panel. The bottom panel shows the number of spikes per second. ADNA, ADN activity. (C) Representative traces of ADN activity at intra-aortic pressures of 0, 50, 100, and 150 mmHg in an expanded time scale. (D) Summary of ADN activity in WT (n = 12) and Ttn3–/– (KO) (n = 7) mice in response to the intra-aortic pressures. Data represent the mean ± SEM. **P < 0.01 and ***P < 0.001, by Student’s t test.