Back to Search
Start Over
Arterial Smooth Muscle Mitochondria Amplify Hydrogen Peroxide Microdomains Functionally Coupled to L-Type Calcium Channels
- Source :
- Circulation research, vol 117, iss 12
- Publication Year :
- 2015
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2015.
-
Abstract
- Rationale: Mitochondria are key integrators of convergent intracellular signaling pathways. Two important second messengers modulated by mitochondria are calcium and reactive oxygen species. To date, coherent mechanisms describing mitochondrial integration of calcium and oxidative signaling in arterial smooth muscle are incomplete. Objective: To address and add clarity to this issue, we tested the hypothesis that mitochondria regulate subplasmalemmal calcium and hydrogen peroxide microdomain signaling in cerebral arterial smooth muscle. Methods and Results: Using an image-based approach, we investigated the impact of mitochondrial regulation of L-type calcium channels on subcellular calcium and reactive oxygen species signaling microdomains in isolated arterial smooth muscle cells. Our single-cell observations were then related experimentally to intact arterial segments and to living animals. We found that subplasmalemmal mitochondrial amplification of hydrogen peroxide microdomain signaling stimulates L-type calcium channels, and that this mechanism strongly impacts the functional capacity of the vasoconstrictor angiotensin II. Importantly, we also found that disrupting this mitochondrial amplification mechanism in vivo normalized arterial function and attenuated the hypertensive response to systemic endothelial dysfunction. Conclusions: From these observations, we conclude that mitochondrial amplification of subplasmalemmal calcium and hydrogen peroxide microdomain signaling is a fundamental mechanism regulating arterial smooth muscle function. As the principle components involved are fairly ubiquitous and positioning of mitochondria near the plasma membrane is not restricted to arterial smooth muscle, this mechanism could occur in many cell types and contribute to pathological elevations of intracellular calcium and increased oxidative stress associated with many diseases.
- Subjects :
- Male
hypertension
Calcium Channels, L-Type
Physiology
1.1 Normal biological development and functioning
Clinical Sciences
Myocytes, Smooth Muscle
chemistry.chemical_element
Cardiorespiratory Medicine and Haematology
Biology
Calcium
Mitochondrion
Muscle, Smooth, Vascular
Article
Calcium in biology
smooth muscle
Rats, Sprague-Dawley
Membrane Microdomains
Underpinning research
Vascular
calcium channels
hypertension myocytes
oxidative stress
Animals
Myocyte
L-type calcium channel
reactive oxygen species
Myocytes
Voltage-dependent calcium channel
T-type calcium channel
Hydrogen Peroxide
Cerebral Arteries
L-Type
Angiotensin II
Mitochondria
Mitochondria, Muscle
Rats
Cell biology
Cardiovascular System & Hematology
Biochemistry
chemistry
Basilar Artery
Muscle
Smooth
Sprague-Dawley
Reactive Oxygen Species
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 15244571 and 00097330
- Volume :
- 117
- Database :
- OpenAIRE
- Journal :
- Circulation Research
- Accession number :
- edsair.doi.dedup.....e1fdb298d76e617b33b9299b22161c78
- Full Text :
- https://doi.org/10.1161/circresaha.115.306996