Brain mitochondrial ATP-insensitive large conductance Ca+2-activated K+ channel properties are altered in a rat model of amyloid-β neurotoxicity

Jafari, Adele; Noursadeghi, Elham; Khodagholi, Fariba; Saghiri, Reza; Sauvé, Rémy; Aliaghaei, Abbas; Eliassi, Afsaneh

doi:10.1016/j.expneurol.2014.12.024

Cited by 26 publications

(12 citation statements)

References 51 publications

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“…Accordingly, in a triple-transgenic mouse model of AD that displays intraneuronal Aβ accumulation prior to the appearance of extracellular Aβ plaques and neurofibrillary tangles (4 months old 3xTg mice; Oddo et al, 2003), spike broadening is observed in neocortical neurons and BK currents cannot be detected unless the mice are first subjected to ECS (Yamamoto et al, 2011). A similar effect of Aβ accumulation on BK channels is also observed in brain mitochondrial inner membranes, as ventricular injection of Aβ 1–42 in rats decreases the abundance of BK α and the open probability of BK channels in this intracellular compartment (Jafari et al, 2015). …”

Section: Role Of Bk Channels In Cns Function and Pathologiesmentioning

confidence: 69%

BK Channels in the Central Nervous System

Contet

Goulding

Kuljis

et al. 2016

International Review of Neurobiology

135

170

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Large conductance Ca2+- and voltage-activated K+ (BK) channels are widely distributed in the postnatal central nervous system (CNS). BK channels play a pleiotropic role in regulating the activity of brain and spinal cord neural circuits by providing a negative feedback mechanism for local increases in intracellular Ca2+ concentrations. In neurons, they regulate the timing and duration of K+ influx such that they can either increase or decrease firing depending on the cellular context, and they can suppress neurotransmitter release from presynaptic terminals. In addition, BK channels located in astrocytes and arterial myocytes modulate cerebral blood flow. Not surprisingly, both loss and gain of BK channel function have been associated with CNS disorders such as epilepsy, ataxia, mental retardation, and chronic pain. On the other hand, the neuroprotective role played by BK channels in a number of pathological situations could potentially be leveraged to correct neurological dysfunction.

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Section: Role Of Bk Channels In Cns Function and Pathologiesmentioning

confidence: 69%

BK Channels in the Central Nervous System

Contet

Goulding

Kuljis

et al. 2016

International Review of Neurobiology

135

170

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“…Mitochondrial potassium channels are distributed in a variety of tissues and cell types . These channels were identified both in tissue containing a high number of mitochondria, such as cardiac muscle and brain, and in tissue less dependent on oxidative phosphorylation, such as endothelium . It is believed that potassium flux through the inner mitochondrial membrane plays a significant role in the cell life/death cycle …”

Section: Discussionmentioning

confidence: 99%

Naringenin as an opener of mitochondrial potassium channels in dermal fibroblasts

Kampa

Kicińska

Jarmuszkiewicz

et al. 2019

Experimental Dermatology

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Flavonoids belong to a large group of polyphenolic compounds that are widely present in plants. Certain flavonoids, including naringenin, have cytoprotective properties. Although the antioxidant effect has long been thought to be a crucial factor accounting for the cellular effects of flavonoids, mitochondrial channels have emerged recently as targets for cytoprotective strategies. In the present study, we characterized interactions between naringenin and the mitochondrial potassium (mitoBKCa and mitoKATP) channels recently described in dermal fibroblasts. With the use of the patch‐clamp technique and mitoplasts isolated from primary human dermal fibroblast cells, our study shows that naringenin in micromolar concentrations leads to an increase in mitoBKCa channel activity. The opening probability of the channel decreased from 0.97 in the control conditions (200 μmol/L Ca2+) to 0.06 at a low Ca2+ level (1 μmol/L) and increased to 0.85 after the application of 10 μmol/L naringenin. Additionally, the activity of the mitoKATP channel increased following the application of 10 μmol/L naringenin. To investigate the effects of naringenin on mitochondrial function, the oxygen consumption of dermal fibroblast cells was measured in potassium‐containing media. The addition of naringenin significantly and dose‐dependently increased the respiratory rate from 5.8 ± 0.2 to 14.0 ± 0.6 nmol O2 × min−1 × mg protein−1. Additionally, a Raman spectroscopy analysis of skin penetration indicated that the naringenin was distributed in all skin layers, including the epidermis and dermis. In this study, we demonstrated that a flavonoid, naringenin, can activate two potassium channels present in the inner mitochondrial membrane of dermal fibroblasts.

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“…In cultured cells, when the concentration of cholesterol ester is increased, there is a proportional elevation in APP [126]. It has been shown that Aβ deposition can be seen in mitochondria and, correspondingly, that Aβ deposition can lead to dysfunctional mitochondria such as mitochondrial swelling, mPTPs, and excessive ROS production [127][128][129][130][131][132][133][134]. Therefore, Aβ has a destructive influence on mitochondrial structure and function.…”

Section: Metabolism and Aβ Depositionmentioning

confidence: 99%

Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

Sun

et al. 2020

Journal of Diabetes Research

113

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As a chronic metabolic disease, diabetes mellitus (DM) is broadly characterized by elevated levels of blood glucose. Novel epidemiological studies demonstrate that some diabetic patients have an increased risk of developing dementia compared with healthy individuals. Alzheimer’s disease (AD) is the most frequent cause of dementia and leads to major progressive deficits in memory and cognitive function. Multiple studies have identified an increased risk for AD in some diabetic populations, but it is still unclear which diabetic patients will develop dementia and which biological characteristics can predict cognitive decline. Although few mechanistic metabolic studies have shown clear pathophysiological links between DM and AD, there are several plausible ways this may occur. Since AD has many characteristics in common with impaired insulin signaling pathways, AD can be regarded as a metabolic disease. We conclude from the published literature that the body’s diabetic status under certain circumstances such as metabolic abnormalities can increase the incidence of AD by affecting glucose transport to the brain and reducing glucose metabolism. Furthermore, due to its plentiful lipid content and high energy requirement, the brain’s metabolism places great demands on mitochondria. Thus, the brain may be more susceptible to oxidative damage than the rest of the body. Emerging evidence suggests that both oxidative stress and mitochondrial dysfunction are related to amyloid-β (Aβ) pathology. Protein changes in the unfolded protein response or endoplasmic reticulum stress can regulate Aβ production and are closely associated with tau protein pathology. Altogether, metabolic disorders including glucose/lipid metabolism, oxidative stress, mitochondrial dysfunction, and protein changes caused by DM are associated with an impaired insulin signal pathway. These metabolic factors could increase the prevalence of AD in diabetic patients via the promotion of Aβ pathology.

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Brain mitochondrial ATP-insensitive large conductance Ca+2-activated K+ channel properties are altered in a rat model of amyloid-β neurotoxicity

Cited by 26 publications

References 51 publications

BK Channels in the Central Nervous System

BK Channels in the Central Nervous System

Naringenin as an opener of mitochondrial potassium channels in dermal fibroblasts

Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

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