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.
View: Text | PDF
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

×

Figure 1

TTN3 is responsible for SA MA currents in aortic arch–projecting NG neurons.

Options: View larger image (or click on image) Download as PowerPoint
TTN3 is responsible for SA MA currents in aortic arch–projecting NG neur...
(A) Immunofluorescence images of TTN3 in NGs isolated from WT and Ttn3–/– (KO) mice. NG neurons were stained with anti-TTN3, -NFH, and -PGP9.5 antibodies. Scale bars: 100 μm. The proportions of colocalization between these markers are shown in the Venn diagrams. (B) Schematic diagram showing injection of the tracer DiI into the aortic arch to selectively label aortic arch–projecting neurons in the NG. (C) Representative traces of 3 types of MA currents in DiI+ NG neurons isolated from WT and KO mice. (D) Summary histogram illustrating 3 types of MA currents characterized in aortic arch–projecting NG neurons based on inactivation kinetics. No response (NR), SA, IA, and RA MA currents are shown. Numbers in parentheses represent the total number of NG neurons tested.