Search results for "Potassium"
showing 10 items of 930 documents
Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex
2016
During the perinatal period, the brain is highly vulnerable to hypoxia and inflammation, which often cause white matter injury and long-term neuronal dysfunction such as motor and cognitive deficits or epileptic seizures. We studied the effects of moderate hypoxia (HYPO), mild systemic inflammation (INFL), or the combination of both (HYPO + INFL) in mouse somatosensory cortex induced during the first postnatal week on network activity and compared it to activity in SHAM control animals. By performing in vitro electrophysiological recordings with multi-electrode arrays from slices prepared directly after injury (P8–10), one week after injury (P13–16), or in young adults (P28–30), we investig…
Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR‐1‐dependent pathway
2019
The aim of this study was to investigate whether telmisartan protects the heart from the ischaemia/reperfusion damage through a local microRNA-1 modulation. Studies on the myocardial ischaemia/reperfusion injury in vivo and on the cardiomyocyte hypoxia/reoxygenation damage in vitro were done. In vivo, male Sprague-Dawley rats administered for 3 weeks with telmisartan 12 mg/kg/d by gastric gavage underwent ischaemia/reperfusion of the left descending coronary artery. In these rats, infarct size measurement, ELISA, immunohistochemistry (IHC) and reverse transcriptase real-time polymerase chain reaction showed that expressions of connexin 43, potassium voltage-gated channel subfamily Q member …
KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern
2019
BACKGROUND: The presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown. METHODS: To identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry. RESULTS: We identified a genome-wide significant (P < 5 × 10(–8)) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discov…
Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors
2020
Abstract Objectives This study evaluated the emergence of mutations associated with integrase strand transfer inhibitors (INSTI) resistance (INSTI-RMs) and the integrase evolution in human immunodeficiency virus type 1 (HIV-1) infected patients treated with this drug class. Methods The emergence of INSTI-RMs and integrase evolution (estimated as genetic distance between integrase sequences under INSTI treatment and before INSTI treatment) were evaluated in 107 INSTI-naive patients (19 drug-naive and 88 drug-experienced) with two plasma genotypic resistance tests: one before INSTI treatment and one under INSTI treatment. A logistic regression analysis was performed to evaluate factors associ…
Pathology-selective antiepileptic effects in the focal freeze-lesion rat model of malformation of cortical development
2021
Malformations of cortical development (MCD) represent a group of rare diseases with severe clinical presentation as epileptic and pharmacoresistant encephalopathies. Morphological studies in tissue from MCD patients have revealed reduced GABAergic efficacy and increased intracellular chloride concentration in neuronal cells as important pathophysiological mechanisms in MCD. Also, in various animal models, alterations of GABAergic inhibition have been postulated as a predominant factor contributing to perilesional hyperexcitability. Along with this line, the NKCC1 inhibitor bumetanide has been postulated as a potential drug for treatment of epilepsy, mediating its antiepileptic effect by red…
Comparative Study of the Effects Exerted by N-Valproyl-L-Phenylalanine and N-valproyl-L-tryptophan on CA1 Hippocampal Epileptiform Activity in Rat
2018
Background: The research on the improvement of epilepsy therapy is constantly growing. Valproyl-LPhenylalanine (VPA-Phen) and N-valproyl-L-tryptophan (VPA-Tryp) were synthesized to increase the antiepileptic efficacy of valproic acid. Methods: VPA-Phen and VPA-Tryp were comparatively tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 mM) of VPA-Phen or VPA-Tryp. Both burst duration and interburst frequency, during and after treatment, were off-line compared with baseline values. For both parameters,…
Potassium channels contribute to the increased sensitivity of the rabbit carotid artery to hydrogen sulfide in diabetes
2019
Abstract Hydrogen sulfide (H2S) is a potential endothelium-derived hyperpolarizing factor (EDHF) and adventitium- or adipocyte-derived relaxing factor (ADRF) which vasorelaxant action is mediated by potassium channels. H2S could also play an important role in the pathophysiology of diabetic cardiovascular complications. The present study has investigated the influence of alloxan-induced diabetes on the role of potassium channels mediating the relaxant response of the rabbit carotid artery to NaHS, a donor of H2S. NaHS (10−8-3 × 10−5 M) relaxed phenylephrine-precontracted carotid arteries, with higher potency in diabetic than in control rabbits. The selective blockers of potassium channels c…
Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome
2020
Mutations in the actively expressed, maternal allele of the imprinted KCNK9 gene cause Birk-Barel intellectual disability syndrome (BBIDS). Using a BBIDS mouse model, we identify here a partial rescue of the BBIDS-like behavioral and neuronal phenotypes mediated via residual expression from the paternal Kcnk9 (Kcnk9pat) allele. We further demonstrate that the second-generation HDAC inhibitor CI-994 induces enhanced expression from the paternally silenced Kcnk9 allele and leads to a full rescue of the behavioral phenotype suggesting CI-994 as a promising molecule for BBIDS therapy. Thus, these findings suggest a potential approach to improve cognitive dysfunction in a mouse model of an impri…
Chronic exercise impairs nitric oxide pathway in rabbit carotid and femoral arteries
2018
KEY POINTS: Some of the beneficial effects of exercise in preventing vascular related diseases are mediated by the enhancement of endothelial function where the role of nitric oxide (NO) is well documented, although the relevance of calcium activated potassium channels is not fully understood. The impact of oxidative stress induced by training on endothelial function remains to be clarified. By evaluating different endothelial vasodilator pathways on two vascular beds in a rabbit model of chronic exercise, we found a decreased NO bioavailability and endothelial nitric oxide synthase expression in both carotid and femoral arteries. Physical training induced carotid endothelial dysfunction as…
Endothelial and neural factors functionally involved in the modulation of noradrenergic vasoconstriction in healthy pig internal mammary artery
2011
The role of endothelial and neural factors as modulators of neurogenic- and noradrenaline-induced vasoconstriction was examined in healthy pig internal mammary artery (IMA). Tetrodotoxin-, guanethidine-sensitive electrical field stimulation (EFS)-, and noradrenaline-elicited contractions were significantly diminished by prazosin (n=8, P0.001) and less so by rauwolscine, indicating functional α₁- and α₂-adrenoceptor-mediated noradrenergic innervation of the IMA. Endothelium removal reduced neurogenic (n=8, P0.01) but augmented noradrenaline responses (n=8, P0.01), suggesting the release of two endothelium-dependent factors with opposite effects. In the presence of endothelium, neurogenic and…