ArticleAmerican journal of physiology. Heart and circulatory physiology2016
Depolarization of mitochondria in neurons promotes activation of nitric oxide synthase and generation of nitric oxide.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
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- Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14.Cell reports · 2023Article
- Ghrelin Action in the PVH of Male Mice: Accessibility, Neuronal Targets, and CRH Neurons Activation.Endocrinology · 2023Article
- Cardiometabolic health, menopausal estrogen therapy and the brain: How effects of estrogens diverge in healthy and unhealthy preclinical models of aging.Frontiers in neuroendocrinology · 2023Review
- The Oxygen and Glucose Deprivation of Immature Cells of the Nervous System Exerts Distinct Effects on Mitochondria, Mitophagy, and Autophagy, Depending on the Cells' Differentiation Stage.Brain sciences · 2023Article
- Diazoxide for Neonatal Hyperinsulinemic Hypoglycemia and Pulmonary Hypertension.Children (Basel, Switzerland) · 2022Review
- Detrimental effects of transient cerebral ischemia on middle cerebral artery mitochondria in female rats.American journal of physiology. Heart and circulatory physiology · 2022Article
- Amyloid AβInternational journal of molecular sciences · 2022Article
- Alternative Targets for Modulators of Mitochondrial Potassium Channels.Molecules (Basel, Switzerland) · 2022Review
- Microvascular dysfunction and kidney disease: Challenges and opportunities?Microcirculation (New York, N.Y. : 1994) · 2021Review
- Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension.Antioxidants & redox signaling · 2021Review
- Cardiac NaThe journal of physiological sciences : JPS · 2019Review
- Mitochondrial depolarization stimulates vascular repair-relevant functions of CD34British journal of pharmacology · 2019Article
- Local anaesthetics upregulate nitric oxide generation in cord blood and adult human neutrophils.Scientific reports · 2019Article
- Gas Signaling Molecules and Mitochondrial Potassium Channels.International journal of molecular sciences · 2018Review
- A novel high-throughput assay for respiration in isolated brain microvessels reveals impaired mitochondrial function in the aged mice.GeroScience · 2018Review
- Connexins and Nitric Oxide Inside and Outside Mitochondria: Significance for Cardiac Protection and Adaptation.Frontiers in physiology · 2018Review
- Molecular Bases of Brain Preconditioning.Frontiers in neuroscience · 2017Article
- Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone.Comprehensive Physiology · 2016Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The diverse signaling events following mitochondrial depolarization in neurons are not clear. We examined for the first time the effects of mitochondrial depolarization on mitochondrial function, intracellular calcium, neuronal nitric oxide synthase (nNOS) activation, and nitric oxide (NO) production in cultured neurons and perivascular nerves. Cultured rat primary cortical neurons were studied on 7-10 days in vitro, and endothelium-denuded cerebral arteries of adult Sprague-Dawley rats were studied ex vivo. Diazoxide and BMS-191095 (BMS), activators of mitochondrial KATP channels, depolarized mitochondria in cultured neurons and increased cytosolic calcium levels. However, the mitochondrial oxygen consumption rate was unaffected by mitochondrial depolarization. In addition, diazoxide and BMS not only increased the nNOS phosphorylation at positive regulatory serine 1417 but also decreased nNOS phosphorylation at negative regulatory serine 847. Furthermore, diazoxide and BMS increased NO production in cultured neurons measured with both fluorescence microscopy and electron spin resonance spectroscopy, which was sensitive to inhibition by the selective nNOS inhibitor 7-nitroindazole (7-NI). Diazoxide also protected cultured neurons against oxygen-glucose deprivation, which was blocked by NOS inhibition and rescued by NO donors. Finally, BMS induced vasodilation of endothelium denuded, freshly isolated cerebral arteries that was diminished by 7-NI and tetrodotoxin. Thus pharmacological depolarization of mitochondria promotes activation of nNOS leading to generation of NO in cultured neurons and endothelium-denuded arteries. Mitochondrial-induced NO production leads to increased cellular resistance to lethal stress by cultured neurons and to vasodilation of denuded cerebral arteries.
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