Tentonin 3/TMEM150C senses blood pressure changes in the aortic arch
Huan-Jun Lu, … , Mi-Ock Lee, Uhtaek Oh
Huan-Jun Lu, … , Mi-Ock Lee, Uhtaek Oh
Published June 2, 2020
Citation Information: J Clin Invest. 2020;130(7):3671-3683. https://doi.org/10.1172/JCI133798.
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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 6

Chemogenetic inhibition or activation of TTN3+ NG neurons causes an increase in MAP and HR, or vice versa.

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Chemogenetic inhibition or activation of TTN3+ NG neurons causes an incr...
(A and C) MAP (A) and HR (C) responses to intraperitoneal injection of CNO into Ttn3Cre mice infected with either AAV-hsyn-DIO-mCherry (gray), AAV-hsyn-DIO-hM3Dq-mCherry (red), or AAV-hsyn-DIO-hM4Di-mCherry (green). Four weeks after the viral infections, the MAP and HR were recorded with a telemetric device in freely moving mice. Data were normalized to the baseline MAP or HR obtained from 0 to 15 minutes before the CNO injection (arrows). (B and D) Averages of MAP and HR changes for 40 minutes after CNO injection (n = 6 mice per group). Data represent the mean ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001, by 1-way ANOVA with Dunnett’s post hoc test.