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KIR4.1

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https://www.readbyqxmd.com/read/28931751/essential-role-of-kir5-1-channels-in-renal-salt-handling-and-blood-pressure-control
#1
Oleg Palygin, Vladislav Levchenko, Daria V Ilatovskaya, Tengis S Pavlov, Oleh M Pochynyuk, Howard J Jacob, Aron M Geurts, Matthew R Hodges, Alexander Staruschenko
Supplementing diets with high potassium helps reduce hypertension in humans. Inwardly rectifying K+ channels Kir4.1 (Kcnj10) and Kir5.1 (Kcnj16) are highly expressed in the basolateral membrane of distal renal tubules and contribute to Na+ reabsorption and K+ secretion through the direct control of transepithelial voltage. To define the importance of Kir5.1 in blood pressure control under conditions of salt-induced hypertension, we generated a Kcnj16 knockout in Dahl salt-sensitive (SS) rats (SSKcnj16-/-). SSKcnj16-/- rats exhibited hypokalemia and reduced blood pressure, and when fed a high-salt diet (4% NaCl), experienced 100% mortality within a few days triggered by salt wasting and severe hypokalemia...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28912901/can-a-selective-serotonin-reuptake-inhibitor-act-as-a-glutamatergic-modulator
#2
Marcos Emilio Frizzo
Sertraline (Zoloft) and fluoxetine (Prozac) are selective serotonin reuptake inhibitors whose antidepressant mechanism of action is classically attributed to an elevation of the extracellular levels of serotonin in the synaptic cleft. However, the biological effects of these drugs seem to be more complex than their traditionally described mechanism of action. Among their actions is the inhibition of different types of Na(+) and K(+) channels, as well as of glutamate uptake activity. The clearance of extracellular glutamate is essential to maintain the central nervous system within physiological conditions, and this excitatory neurotransmitter is removed from the synaptic cleft by astrocyte transporters...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/28835827/epilepsy-ataxia-sensorineural-deafness-tubulopathy-syndrome-in-a-european-child-with-kcnj10-mutations-a-case-report
#3
Antigone Papavasiliou, Katerina Foska, John Ioannou, Mato Nagel
BACKGROUND: Epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome is a multi-organ disorder that links to autosomal recessive mutations in the KCNJ10 gene, which encodes for the Kir4.1 potassium channel. It is mostly described in consanguineous, non-European families. CASE REPORT: A European male of non-consanguineous birth, with early-onset, static ataxic motor disorder, intellectual disability and epilepsy, imitating cerebral palsy, presented with additional findings of renal tubulopathy, sensorineural deafness and normal neuroimaging leading to the diagnosis of epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome...
2017: SAGE open medical case reports
https://www.readbyqxmd.com/read/28747464/lethal-digenic-mutations-in-the-k-channels-kir4-1-kcnj10-and-slack-kcnt1-associated-with-severe-disabling-seizures-and-neurodevelopmental-delay
#4
Sonia Majed Hasan, Ameera Balobaid, Alessandro Grottesi, Omar Dabbagh, Marta Cenciarini, Rifaat Rawashdeh, Afaf Al-Sagheir, Cecilia Bove, Lara Macchioni, Mauro Pessia, Mohammed Al-Owain, Maria Cristina D'Adamo
A 2-year-old boy presented profound developmental delay, failure to thrive, ataxia, hypotonia and tonic-clonic seizures that caused the death of the patient. Targeted and whole-exome sequencing revealed two heterozygous missense variants: a novel mutation in KCNJ10 gene that encodes for the inwardly-rectifying K(+) channel Kir4.1 and another previously characterized mutation in KCNT1 that encodes for the Na(+)-activated K(+) channel known as Slo2.2 or SLACK. The objectives of this study were to perform the clinical and genetic characterization of the proband and his family and to examine the functional consequence of the Kir4...
July 26, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28744903/activity-dependent-astrocyte-swelling-is-mediated-by-ph-regulating-mechanisms
#5
Brian Roland Larsen, Nanna MacAulay
During neuronal activity in the mammalian brain, the K(+) released into the synaptic space is initially buffered by the astrocytic compartment. In parallel, the extracellular space (ECS) shrinks, presumably due to astrocytic cell swelling. With the Na(+) /K(+) /2Cl(-) cotransporter and the Kir4.1/AQP4 complex not required for the astrocytic cell swelling in the hippocampus, the molecular mechanisms underlying the activity-dependent ECS shrinkage have remained unresolved. To identify these molecular mechanisms, we employed ion-sensitive microelectrodes to measure changes in ECS, [K(+) ]o and [H(+) ]o /pHo during electrical stimulation of rat hippocampal slices...
July 26, 2017: Glia
https://www.readbyqxmd.com/read/28679838/fluorocitrate-mediated-depolarization-of-astrocytes-in-the-retrotrapezoid-nucleus-stimulates-breathing
#6
Cleyton R Sobrinho, Christopher M Gonçalves, Ana C Takakura, Daniel K Mulkey, Thiago S Moreira
Evidence indicates that CO2/H(+)-evoked ATP released from retrotrapezoid nucleus (RTN) astrocytes modulates the activity of CO2-sensitive neurons. RTN astrocytes also sense H(+) by inhibition of Kir4.1 channels; however, the relevance of this pH-sensitive current remains unclear since ATP release appears to involve CO2-dependent gating of connexin 26 hemichannels. Considering that depolarization mediated by H(+) inhibition of Kir4.1 channels is expected to increase sodium bicarbonate cotransporter (NBC) conductance and favor Ca(2+) influx via the sodium calcium exchanger (NCX), we hypothesize that depolarization in the presence of CO2 is sufficient to facilitate ATP release and enhance respiratory output...
September 1, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28615682/improved-retinal-function-in-rcs-rats-after-suppressing-the-over-activation-of-mglur5
#7
Jiaman Dai, Yan Fu, Yuxiao Zeng, Shiying Li, Zheng Qin Yin
Müller cells maintain retinal synaptic homeostasis by taking up glutamate from the synaptic cleft and transporting glutamine back to the neurons. To study the interaction between Müller cells and photoreceptors, we injected either DL-α-aminoadipate or L-methionine sulfoximine-both inhibitors of glutamine synthetase-subretinally in rats. Following injection, the a-wave of the electroretinogram (ERG) was attenuated, and metabotropic glutamate receptor 5 (mGluR5) was activated. Selective antagonism of mGluR5 by 2-methyl-6-(phenylethynyl)-pyridine increased the ERG a-wave amplitude and also increased rhodopsin expression...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28597918/inflammation-in-the-developing-rat-modulates-astroglial-reactivity-to-seizures-in-the-mature-brain
#8
Zuzanna Setkowicz, Emilia Kosonowska, Krzysztof Janeczko
Astrocytes participate in neuronal development and excitability, and produce factors enhancing or suppressing inflammatory processes occurring due to neurodegenerative diseases, such as epilepsy. Seizures, in turn, trigger the release of inflammatory mediators, causing structural and functional changes in the brain. Therefore, it appears reasonable to determine whether generalized inflammation at developmental periods can affect astrocyte reactivity to epileptic seizures occurring in the adult brain. Lipopolysaccharide (LPS) was injected in 6- or 30-day-old rats (P6 or P30, respectively)...
June 9, 2017: Journal of Anatomy
https://www.readbyqxmd.com/read/28577853/loss-of-transcriptional-activation-of-the-potassium-channel-kir5-1-by-hnf1%C3%AE-drives-autosomal-dominant-tubulointerstitial-kidney-disease
#9
Andreas Kompatscher, Jeroen H F de Baaij, Karam Aboudehen, Anke P W M Hoefnagels, Peter Igarashi, René J M Bindels, Gertjan J C Veenstra, Joost G J Hoenderop
Hepatocyte nuclear factor 1 homeobox B (HNF1β) is an essential transcription factor for the development and functioning of the kidney. Mutations in HNF1β cause autosomal dominant tubulointerstitial kidney disease characterized by renal cysts and maturity-onset diabetes of the young (MODY). Moreover, these patients suffer from a severe electrolyte phenotype consisting of hypomagnesemia and hypokalemia. Until now, genes that are regulated by HNF1β are only partially known and do not fully explain the phenotype of the patients...
May 31, 2017: Kidney International
https://www.readbyqxmd.com/read/28576938/neuroimmune-glia-interactions-in-the-sensory-ganglia-account-for-the-development-of-acute-herpetic-neuralgia
#10
Jaqueline R Silva, Alexandre H Lopes, Jhimmy Talbot, Nerry T Cecilio, Mateus F Rossato, Rangel L Silva, Guilherme R Souza, Cassia R Silva, Guilherme Lucas, Benedito A Fonseca, Eurico Arruda, Jose C Alves-Filho, Fernando Q Cunha, Thiago M Cunha
Herpetic neuralgia is the most important symptom of herpes zoster disease, which is caused by Varicella zoster Nevertheless, the pathophysiological mechanisms involved in herpetic neuralgia are not totally elucidated. Here, we examined the neuroimmune interactions at the sensory ganglia that account for the genesis of herpetic neuralgia using a murine model of Herpes Simplex Virus Type-1 (HSV-1) infection. The cutaneous HSV-1 infection of mice results in the development of a zosteriform-like skin lesion followed by a time-dependent increase in pain-like responses (mechanical allodynia)...
July 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28562601/multifunctional-glial-support-by-semper-cells-in-the-drosophila-retina
#11
Mark A Charlton-Perkins, Edward D Sendler, Elke K Buschbeck, Tiffany A Cook
Glial cells play structural and functional roles central to the formation, activity and integrity of neurons throughout the nervous system. In the retina of vertebrates, the high energetic demand of photoreceptors is sustained in part by Müller glia, an intrinsic, atypical radial glia with features common to many glial subtypes. Accessory and support glial cells also exist in invertebrates, but which cells play this function in the insect retina is largely undefined. Using cell-restricted transcriptome analysis, here we show that the ommatidial cone cells (aka Semper cells) in the Drosophila compound eye are enriched for glial regulators and effectors, including signature characteristics of the vertebrate visual system...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28548026/low-reliability-of-anti-kir4-183-120-peptide-auto-antibodies-in-multiple-sclerosis-patients
#12
Mariapaola Marino, Giovanni Frisullo, Gabriele Di Sante, Daniela Maria Samengo, Carlo Provenzano, Massimiliano Mirabella, Giovambattista Pani, Francesco Ria, Emanuela Bartoccioni
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease for which auto-antibodies fully validated as diagnostic and prognostic biomarkers are widely desired. Recently, an immunoreactivity against the inward rectifying potassium channel 4.1 (KIR4.1) has been reported in a large proportion of a group of MS patients, with amino acids 83-120 being the major epitope. Moreover, a strong correlation between anti-KIR4.183-120 and anti-full-length-protein auto-antibodies titer was reported...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28526685/differences-in-molecular-mechanisms-of-k-clearance-in-the-auditory-sensory-epithelium-of-birds-and-mammals
#13
Viviane Wilms, Chris Söffgen, Hans Gerd Nothwang
Mechanoelectrical transduction in the vertebrate inner ear is a highly conserved mechanism depending on K(+) influx into hair cells. Here, we investigated the molecular underpinnings of subsequent K(+) recycling in the chicken basilar papilla and compared it with those in the mammalian auditory sensory epithelium. Like mammals, the avian auditory hair cell uses KCNQ4, KCNMA1, and KCNMB1 as K(+) efflux systems. Expression of KCNQ1 and KCNE1 suggests an additional efflux apparatus in avian hair cells. Marked differences were observed for K(+) clearance...
May 19, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28520217/the-gene-encoding-the-inwardly-rectifying-potassium-channel-kir4-1-may-be-involved-in-sudden-infant-death-syndrome
#14
Siri H Opdal, Åshild Vege, Arne Stray-Pedersen, Torleiv O Rognum
AIM: Disturbances in brain function and development may play a role in sudden infant death syndrome (SIDS). This Norwegian study aimed to test the hypothesis that specific variants of genes involved in water transport and potassium homeostasis would be predisposing factors for SIDS. METHODS: Genetic variation in the genes encoding aquaporin-4 (AQP4), Kir4.1 (KCNJ10) and α-syntrophin was analysed in 171 SIDS cases (62.6% male) with a median age of 15.5 (2-52) weeks and 398 adult controls (70...
May 18, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28460049/tumor-necrosis-factor-alpha-tnf-%C3%AE-disrupts-kir4-1-channel-expression-resulting-in-m%C3%A3-ller-cell-dysfunction-in-the-retina
#15
Iraj Hassan, Qianyi Luo, Sreeparna Majumdar, James M Dominguez, Julia V Busik, Ashay D Bhatwadekar
Purpose: Diabetic patients often are affected by vision problems. We previously identified diabetic retinopathy (DR) as a disease of clock gene dysregulation. TNF-α, a proinflammatory cytokine, is known to be elevated in DR. Müller cells maintain retinal water homeostasis and K+ concentration via Kir4.1 channels. Notably, Kir4.1 expression is reduced in diabetes; however, the interplay of TNF-α, Kir4.1, and clock genes in Müller cells remains unknown. We hypothesize that the Kir4...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28445150/modulation-of-the-inwardly-rectifying-potassium-channel-kir4-1-by-the-pro-invasive-mir-5096-in-glioblastoma-cells
#16
Dominique Thuringer, Gaetan Chanteloup, Jonathan Boucher, Nicolas Pernet, Christophe Boudesco, Gaetan Jego, Aurelien Chatelier, Patrick Bois, Jessica Gobbo, Laurent Cronier, Eric Solary, Carmen Garrido
Inwardly rectifying potassium channels (Kir), and especially the barium-sensitive Kir4.1 encoded by KCNJ10, are key regulators of glial functions. A lower expression or mislocation of Kir4.1 is detected in human brain tumors. MicroRNAs participate in the regulation of ionic channels and associated neurologic disorders. Here, we analyze effects of miR-5096 on the Kir4.1 expression and function in two glioblastoma cell lines, U87 and U251. Using whole-cell patch-clamp and western-blot analysis, we show that cell loading with miR-5096 decreases the Kir4...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414733/absence-of-antibodies-against-kir4-1-in-multiple-sclerosis-a-three-technique-approach-and-systematic-review
#17
Miquel Navas-Madroñal, Ana Valero-Mut, María José Martínez-Zapata, Manuel Javier Simón-Talero, Sebastián Figueroa, Nuria Vidal-Fernández, Mariana López-Góngora, Antonio Escartín, Luis Querol
INTRODUCTION: Antibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to replicate this association. The detection of these antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse technical approaches may account for the disparity of results. We aimed to replicate the association using three different approaches to overcome the technical limitations of a single technique...
2017: PloS One
https://www.readbyqxmd.com/read/28395711/-il-1%C3%AE-promotes-the-proliferation-of-astrocytes-and-downregulates-the-expression-of-kir4-1
#18
Meiqun Sun, Hongtao Wang, Qi Qi, Haiqin Yan, Weiyan Zou, Xingwu Dong, Zihai Wang, Jinghao Wang, Xiaojing Wang
Objective To explore the impact of IL-1β on the proliferation of astrocytes and the expression of the inwardly rectifying potassium channel 4.1 (Kir4.1) in astrocytes. Methods Astrocytes were isolated from cerebral cortex of newborn SD rats and cultured in the presence of IL-1β or IL-1β combined with interleukin-1 receptor antagonist (IL-1Ra). The effect of IL-1β on the cell cycle of astrocytes was measured with flow cytometry; the level of Kir4.1 mRNA was determined by quantitative real-time PCR. The level of Kir4...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28391264/anti-kir4-1-antibodies-in-chinese-patients-with-central-nervous-system-inflammatory-demyelinating-disorders
#19
Rong Zhong, Junyan Liang, Ailin Tao, Linzhan Wu, Xinguang Yang, Huiming Xu, Qingmei Huang, Shunzhi Zhuang, Youming Long, Cong Gao
OBJECTIVES: The aim of this study was to explore the frequency of KIR4.1 antibodies in patients with multiple sclerosis (MS) and in control groups using a cell-based assay. MATERIALS AND METHODS: A transfected HEK-293A cell line expressing KIR4.1 was established to test for the presence of KIR4.1 antibodies in blood serum. We tested 904 subjects, including 188 patients with MS, 264 patients with neuromyelitis optica spectrum disorders (NMOSD), 209 patients with other inflammatory neurologic disease (OIND), 203 patients with other noninflammatory neurological disease (OND), and 40 healthy controls...
2016: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28365586/enac-and-romk-activity-are-inhibited-in-the-dct2-cnt-of-tgwnk4-phaii-mice
#20
Chengbiao Zhang, Lijun Wang, Xiao-Tong Su, Junhui Zhang, Dao-Hong Lin, Wen-Hui Wang
Mice transgenic for genomic segments harboring PHAII (pseudohypoaldosteronism type II) mutant Wnk4 (with-No-Lysine kinase 4) (TgWnk4(PHAII)) have hyperkalemia which is currently believed to be the result of high activity of Na-Cl cotransporter (NCC). This leads to decreasing Na(+) delivery to the distal nephron segment including late distal convoluted tubule (DCT) and connecting tubule (CNT). Since epithelial Na(+) channel (ENaC) and renal outer medullary K(+) channel (ROMK or Kir4.1) are expressed in the late DCT and play an important role in mediating K(+) secretion, the aim of the present study is to test whether ROMK and ENaC activity in the DCT/CNT are also compromised in the mice expressing PHAII mutant Wnk4...
April 1, 2017: American Journal of Physiology. Renal Physiology
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