1. Hif1α-dependent mitochondrial acute O 2 sensing and signaling to myocyte Ca 2+ channels mediate arterial hypoxic vasodilation.
- Author
-
Moreno-Domínguez A, Colinas O, Arias-Mayenco I, Cabeza JM, López-Ogayar JL, Chandel NS, Weissmann N, Sommer N, Pascual A, and López-Barneo J
- Subjects
- Animals, Mice, Signal Transduction, Male, Hypoxia metabolism, Mice, Inbred C57BL, Arteries metabolism, Calcium Channels, L-Type metabolism, Calcium Channels, L-Type genetics, Mice, Knockout, Electron Transport, Calcium Channels metabolism, Calcium Channels genetics, Vasodilation, Mitochondria metabolism, Oxygen metabolism, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Hypoxia-Inducible Factor 1, alpha Subunit genetics
- Abstract
Vasodilation in response to low oxygen (O
2 ) tension (hypoxic vasodilation) is an essential homeostatic response of systemic arteries that facilitates O2 supply to tissues according to demand. However, how blood vessels react to O2 deficiency is not well understood. A common belief is that arterial myocytes are O2 -sensitive. Supporting this concept, it has been shown that the activity of myocyte L-type Ca2+ channels, the main ion channels responsible for vascular contractility, is reversibly inhibited by hypoxia, although the underlying molecular mechanisms have remained elusive. Here, we show that genetic or pharmacological disruption of mitochondrial electron transport selectively abolishes O2 modulation of Ca2+ channels and hypoxic vasodilation. Mitochondria function as O2 sensors and effectors that signal myocyte Ca2+ channels due to constitutive Hif1α-mediated expression of specific electron transport subunit isoforms. These findings reveal the acute O2 -sensing mechanisms of vascular cells and may guide new developments in vascular pharmacology., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF