Role of Potassium Channels in Cerebral Blood Vessels

Kitazono, Takanari; Faraci, Frank M.; Taguchi, Hisao; Heistad, D D

doi:10.1161/01.str.26.9.1713

Cited by 167 publications

(88 citation statements)

References 143 publications

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“…Moreover, the paradigm for GRK-initiated desensitization of only agonist-occupied receptors (12) is consonant with the homologous ET A -R and ET B -R desensitization observed in a multitude of experimental systems (5)(6)(7)(8)(9)(10)(11). The rapid rate of receptor/effector desensitization observed in some of these systems (4,5,(7)(8)(9)11) is also consistent with a GRK-initiated mechanism (15,16). In this study, the use of dominant-negative GRK2 to inhibit both agonistinduced phosphorylation and desensitization of the ET A -R demonstrates that these events are indeed mediated by a GRK mechanism (18,21,35,36).…”

Section: Discussionmentioning

confidence: 71%

“…This desensitization may be particularly important in the regulation of ET-R-mediated signaling, since endothelins bind their receptors essentially irreversibly under physiological conditions (2). In several cell types or tissues, this desensitization has been characterized phenomenologically as homologous, or receptorspecific (5)(6)(7)(8)(9)(10)(11), but the molecular mechanisms effecting this desensitization remain to be elucidated.…”

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confidence: 99%

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Phosphorylation and Desensitization of Human Endothelin A and B Receptors

Freedman

Ament

Oppermann

et al. 1997

Journal of Biological Chemistry

174

160

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Although endothelin-1 can elicit prolonged physiologic responses, accumulating evidence suggests that rapid desensitization affects the primary G protein-coupled receptors mediating these responses, the endothelin A and B receptors (ET A -R and ET B -R). The mechanisms by which this desensitization proceeds remain obscure, however. Because some intracellular domain sequences of the ET A -R and ET B -R differ substantially, we tested the possibility that these receptor subtypes might be differentially regulated by G protein-coupled receptor kinases (GRKs). Homologous, or receptor-specific, desensitization occurred within 4 min both in the ET A -R-expressing A10 cells and in 293 cells transfected with either the human ET A -R or ET B -R. In 293 cells, this desensitization corresponded temporally with agonistinduced phosphorylation of each receptor, assessed by receptor immunoprecipitation from 32 P i -labeled cells. Agonist-induced receptor phosphorylation was not substantially affected by PKC inhibition but was reduced 40% (p < 0.03) by GRK inhibition, effected by a dominant negative GRK2 mutant. Inhibition of agonist-induced phosphorylation abrogated agonist-induced ET A -R desensitization. Overexpression of GRK2, -5, or -6 in 293 cells augmented agonist-induced ET-R phosphorylation ϳ2-fold (p < 0.02), but each kinase reduced receptorpromoted phosphoinositide hydrolysis differently. While GRK5 inhibited ET-R signaling by only ϳ25%, GRK2 inhibited ET-R signaling by 80% (p < 0.01). Congruent with its superior efficacy in suppressing ET-R signaling, GRK2, but not GRK5, co-immunoprecipitated with the ET-Rs in an agonist-dependent manner. We conclude that both the ET A -R and ET B -R can be regulated indistinguishably by GRK-initiated desensitization. We propose that because of its affinity for ET-Rs demonstrated by co-immunoprecipitation, GRK2 is the most likely of the GRKs to initiate ET-R desensitization.A variety of vital cardiovascular and developmental functions are mediated through the G protein 1 -coupled, heptahelical endothelin A and endothelin B receptors (ET A -R and ET B -R) (1, 2). Like many G protein-coupled receptor signaling systems (3), the receptor/G q /phospholipase C system(s) activated by the ET A -R and ET B -R have demonstrated diminishing responsiveness to prolonged stimulation (4 -11). This desensitization may be particularly important in the regulation of ET-R-mediated signaling, since endothelins bind their receptors essentially irreversibly under physiological conditions (2). In several cell types or tissues, this desensitization has been characterized phenomenologically as homologous, or receptorspecific (5-11), but the molecular mechanisms effecting this desensitization remain to be elucidated.For a growing number of G protein-coupled receptor signaling systems, phosphorylation of the receptor on serine and threonine residues appears to be an important mechanism of desensitization (3, 12). This phosphorylation can be accomplished by at least two classes of protein kinases: (i) second me...

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Section: Discussionmentioning

confidence: 71%

mentioning

confidence: 99%

Phosphorylation and Desensitization of Human Endothelin A and B Receptors

Freedman

Ament

Oppermann

et al. 1997

Journal of Biological Chemistry

174

160

View full text Add to dashboard Cite

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“…Intracerebral calcium, intimately regulated by vitamin D, interferes with vessel activation. Vessel relaxation is heavily influenced by ATP-sensitive potassium channels (delayed rectifier and inward rectifier potassium channel) but also by calcium-activated potassium channels [257][258]. Mediated by cAMP, calcium activated-potassium channels seem to be involved in the negative "feedback system to regulate vascular tone" [257].…”

Section: Vitamin D Deficiency and Neurodegenerative Diseasesmentioning

confidence: 99%

“…Vessel relaxation is heavily influenced by ATP-sensitive potassium channels (delayed rectifier and inward rectifier potassium channel) but also by calcium-activated potassium channels [257][258]. Mediated by cAMP, calcium activated-potassium channels seem to be involved in the negative "feedback system to regulate vascular tone" [257]. It seems that in atherosclerosis models, there is a major impairment of calcium-activated potassium channels in mainstream vessels [259].…”

Section: Vitamin D Deficiency and Neurodegenerative Diseasesmentioning

confidence: 99%

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Moretti

Morelli

Caruso

2018

Preprint

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It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA).Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration.Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions.We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation. Peer-reviewed version available at Int. J. Mol. Sci. 2018, 19, 2245 doi:10.3390/ijms19082245 3 SEARCH STRATEGY AND SELECTION CRITERIAWe searched MEDLINE using the search terms: "vitamin D central nervous system" , both "vitamin D" and "central nervous system"; "vitamin D immune system/response", both "vitamin D" and "immune system" or "immune response"; "vitamin D multiple sclerosis risk", both "vitamin D" and "multiple sclerosis risk"; "vitamin D multiple sclerosis relapse", both "vitamin D" and "multiple sclerosis relapse"; "vitamin D multiple sclerosis magnetic resonance imaging", both "vitamin D" and "multiple sclerosis magnetic resonance imaging"; "vitamin D multiple sclerosis disability", both "vitamin D" and "multiple sclerosis disability"; "vitamin D supplementation/therapy/treatment multiple sclerosis", both "vitamin D supplementation" or "vitamin D therapy" or "vitamin D treatment" and "multiple sclerosis"; "vascular dementia", both as -vascular-and -dementia-, "subcortical vascular dementia", both assubcortical-and -dementia-, "Alzheimer's disease", "pathogenesis neurodegeneration" "amyloid", "cholinergic afferents", "arteriolosclerosis", "cerebral flow regulation", "stroke". Publications were selected mostly form the past 20years, but did not exclude frequently referenced and highly regarded older publications. . Congress abstracts and isolated case reports were not considered. We searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Review articles and book chapters are cited to provide with ...

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“…K Ca channels can be activated by elevations in intracellular Ca 2ϩ through the physiological range as well as via membrane depolarization (11,12,24,30,43). K Ca channels have the biophysical characteristics of single-channel conductance of ϳ250 pS in symmetrical K ϩ (12,30).…”

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confidence: 99%

Opening of Ca²⁺-activated K⁺ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice

Wang¹,

Yin²,

Xi³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Opening of Ca2+-activated K+ (KCa) channels has been shown to confer early cardioprotection. It is unknown whether the opening of these channels also induces delayed cardioprotection. In addition, we determined the involvement of nitric oxide synthases (NOSs), which have been implicated in cardioprotection induced by opening of mitochondrial ATP-sensitive K+ (KATP) channels. Adult male ICR mice were pretreated with the KCa-channel opener NS-1619 either 10 min or 24 h before 30 min of global ischemia and 60 min of reperfusion (I/R) in Langendorff mode. Infusion of NS-1619 (10 μM) for 10 min before I/R led to smaller infarct sizes as compared with the vehicle (DMSO)-treated group ( P < 0.05). This infarct-limiting effect of NS-1619 was associated with improvement in ventricular functional recovery after I/R. The NS-1619-induced protection was abolished by coadministration with the KCa-channel blocker paxilline (1 μM). Similarly, pretreatment with NS-1619 (1 mg/kg ip) induced delayed protection 24 h later ( P < 0.05). Interestingly, the NS-1619-induced late protection was not blocked by the NOS inhibitor Nω-nitro-l-arginine methyl ester (15 mg/kg ip). Unlike diazoxide (the opener of mitochondrial KATP channels), NS-1619 did not increase the expression of inducible or endothelial NOS. Western blot analysis demonstrated the existence of α- and β-subunits of KCa channels in mouse heart tissue. We conclude that opening of KCa channels leads to both early and delayed preconditioning effects through a mechanism that is independent of nitric oxide.

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Role of Potassium Channels in Cerebral Blood Vessels

Abstract: Activation of potassium channels is a major mechanism of cerebral vasodilatation. Alteration of activity of potassium channels and impairment of vasodilatation may contribute to the development or maintenance of cerebral ischemia or vasospasm.

Cited by 167 publications

References 143 publications

Phosphorylation and Desensitization of Human Endothelin A and B Receptors

Phosphorylation and Desensitization of Human Endothelin A and B Receptors

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Opening of Ca²⁺-activated K⁺ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice

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Role of Potassium Channels in Cerebral Blood Vessels

Abstract: Activation of potassium channels is a major mechanism of cerebral vasodilatation. Alteration of activity of potassium channels and impairment of vasodilatation may contribute to the development or maintenance of cerebral ischemia or vasospasm.

Cited by 167 publications

References 143 publications

Phosphorylation and Desensitization of Human Endothelin A and B Receptors

Phosphorylation and Desensitization of Human Endothelin A and B Receptors

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Opening of Ca2+-activated K+ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice

Contact Info

Product

Resources

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Opening of Ca²⁺-activated K⁺ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice