potassium channel

Klotho regulates many pathways in the aging process, but it remains unclear how it is physiologically regulated. Because Klotho is synthesized, cleaved, and released from the kidney; activates the chief urinary K+ secretion channel (ROMK) and stimulates urinary K+ secretion, we explored if Klotho protein is regulated by dietary K+ and the potassium-regulatory hormone, Aldosterone. Klotho protein along the nephron was evaluated in humans and in wild-type (WT) mice; and in mice lacking components of Aldosterone signaling, including the Aldosterone-Synthase KO (AS-KO) and the Mineralocorticoid-Receptor KO (MR-KO) mice...

OBJECTIVE: To investigate the role of NN414, a selective KATP channel opener for the Kir6.2/SUR1 channel subtype found in neurons and β-pancreatic cells, in inducing migraine attacks in individuals with migraine without aura. METHODS: Thirteen participants were randomly allocated to receive NN414 and placebo on two days separated by at least one week. The primary endpoint was the difference in the incidence of migraine attacks after NN414 compared with placebo...

BACKGROUND: G protein-coupled receptors play a critical role in atrial fibrillation (AF). Spexin is a novel ligand of galanin receptors (GALRs). In this study, we investigated the regulation of spexin and GALRs on AF and the underlying mechanisms. METHODS: Global spexin knockout (SPX-KO) and cardiomyocyte-specific GALRs knockout (GALR-cKO) mice underwent burst pacing electrical stimulation. Optical mapping was used to determine atrial conduction velocity and action potential duration...

The voltage-gated Kv3.1/KCNC1 channel is abundantly expressed in fast-spiking principal neurons and GABAergic inhibitory interneurons throughout the ascending auditory pathway and in various brain regions. Inactivating mutations in the KCNC1 gene lead to forms of epilepsy and a decline in the expression of the Kv3.1 channel is involved in age-related hearing loss. As oxidative stress plays a fundamental role in the pathogenesis of epilepsy and age-related hearing loss, we hypothesized that an oxidative insult might affect the function of this channel...

Throughout the brain, astrocytes form networks mediated by gap junction channels that promote the activity of neuronal ensembles. Although their inputs on neuronal information processing are well established, how molecular gap junction channels shape neuronal network patterns remains unclear. Here, using astroglial connexin-deficient mice, in which astrocytes are disconnected and neuronal bursting patterns are abnormal, we show that astrocyte networks strengthen bursting activity via dynamic regulation of extracellular potassium levels, independently of glutamate homeostasis or metabolic support...

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+ . Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+ , as supported by X-ray crystallography and ICP-MS...

In solvothermal reactions of Zn(NO3)2×6H2O with K(H2mF-BTC) or K(H2dF-BTC) in DMF/ethanol or DMA/ethanol solvent mixtures, single crystals of the MOFs UoC-7(1F) and UoC-7(2F) were obtained crystallizing in the hexagonal space group P63/m (no. 176) (H3BTC: 1,3,5-benzenetricarboxylic acid; mF-/dF: mono-/difluoro; DMF: N,N-dimethylformamide; DMA: N,N-dimethylacetamide; UoC: University of Cologne). According to the general composition [(CH3)2NH2][K2Zn3(mF-/dF-BTC)3(H2O)]×solvent, UoC-7 consists of an anionic bimetallic framework...

BACKGROUND: The endocannabinoid system plays important roles in various systems, including the genitourinary system; however, its mechanism of action is not fully understood. OBJECTIVES: This study aimed to investigate the direct relaxant effects of anandamide and its possible mechanisms in isolated rat bladder and vas deferens tissues. METHODS: Twenty-one adult male Wistar albino rats were used. Bladder and vas deferens (prostatic and epididymal portions) tissues were mounted in 10 mL of organ baths...

BACKGROUND: The objective of the study was to design and synthesize a series of N-(6-substituted-1,3-benzothiazole- 2-yl)-2-{[6-(3-substitutedphenyl)-5-cyano-2-sulfanylpyrimidine-4-yl)]amino}acetamide derivatives BPD (1-15) that contains key pharmacophores required for anticonvulsant action. METHODS: The titled compounds (BPD 1-15) were synthesized by reacting 2-substituted-N-(6-chlorobenzo[d]thiazol2-yl)acetamide with 4-amino-6-(4-substituted phenyl)-2-mercapto pyrimidine 5-carbonitrile in the presence of potassium carbonate and dry acetone...

BACKGROUND: Long QT syndrome (LQTS) is a cardiac channelopathy characterized by impaired myocardial repolarization that predisposes to life-threatening arrhythmias. This study aimed to elucidate the genetic basis of LQTS in an affected Iranian family using whole exome sequencing (WES). METHODS: A 37-year-old woman with a personal and family history of sudden cardiac arrest and LQTS was referred for genetic study after losing her teenage daughter due to sudden cardiac death (SCD)...

Introducing a donor-acceptor (D-A) unit is an effective approach to facilitate charge transfer in polymeric carbon nitride (PCN) and enhance photocatalytic performance. However, the introduction of hetero-molecules can lead to a decrease in crystallinity, limiting interlayer charge transfer and inhibiting further improvement. In this study, we constructed a novel D-A type carbon nitride with significantly higher crystallinity and a bi-directional charge transfer channel, which was achieved through 2,5-thiophenedicarboxylic acid (2,5-TDCA)-assisted self-assembly followed by KCl-templated calcination...

It is believed that antivenoms play a crucial role in neutralizing venoms. However, uncontrolled clinical effects appear in patients stung by scorpions after the injection of antivenom. In this research, non-neutralized components of the venom of the Iranian scorpion Odonthobuthus doriae were analyzed after interacting with the commercial antivenom available in the market. The venom and antivenom interaction was performed, then centrifuged, and the supernatant was analyzed by high-performance liquid chromatography (HPLC)...

KCNH5 gene encodes for the voltage-gated potassium channel protein Kv10.2. Here, we investigated the clinical features of developmental and epileptic encephalopathy (DEE) in five Chinese pediatric patients with a missense mutation (p.R327H) in KCNH5 gene. These patients had undergone video EEG to evaluate background features and epileptiform activity, as well as 3.0 T MRI scans for structural analysis and intelligence assessments using the Gesell Developmental Observation or Wechsler Intelligence Scale for Children...

Methamphetamine use disorder (MUD) is a neuropsychiatric disorder characterized by binge drug taking episodes, intervals of abstinence, and relapses to drug use even during treatment. MUD has been modeled in rodents and investigators are attempting to identify its molecular bases. Preclinical experiments have shown that different schedules of methamphetamine self-administration can cause diverse transcriptional changes in the dorsal striatum of Sprague-Dawley rats. In the present review, we present data on differentially expressed genes (DEGs) identified in the rat striatum following methamphetamine intake...

Potassium ion transport across myocardial cell membrane is essential for type 2 long QT syndrome (LQT2). However, the dysfunction of potassium ion transport due to genetic mutations limits the therapeutic effect in treating LQT2. Biomimetic ion channels that selectively and efficiently transport potassium ions across the cellular membranes are promising for the treatment of LQT2. To corroborate this, we synthesized a series of foldamer-based ion channels with different side chains, and found a biomimetic ion channel of K+ (BICK ) with the highest transport activity among them...

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BACKGROUND: Delamanid (DLM) is a relatively new drug for drug-resistant tuberculosis (DR-TB) that has been used in Indonesia since 2019 despite its limited safety data. DLM is known to inhibit hERG potassium channel with the potential to cause QT prolongation which eventually leads to Torsades de pointes (TdP). OBJECTIVE: This study aims to analyse the changes of QTc interval in DR-TB patients on DLM regimen compared to shorter treatment regimens (STR). METHODS: A retrospective cohort was implemented on secondary data obtained from two participating hospitals...

The gain-of-function mutation in the TALK-1 K+ channel (p.L114P) is associated with maturity-onset diabetes of the young (MODY). TALK-1 is a key regulator of β-cell electrical activity and glucose-stimulated insulin secretion. The KCNK16 gene encoding TALK-1 is the most abundant and β-cell-restricted K+ channel transcript. To investigate the impact of KCNK16 L114P on glucose homeostasis and confirm its association with MODY, a mouse model containing the Kcnk16 L114P mutation was generated. Heterozygous and homozygous Kcnk16 L114P mice exhibit increased neonatal lethality in the C57BL/6J and the CD-1 (ICR) genetic background, respectively...

BACKGROUND: Propofol is a widely used intravenous hypnotic. Dosing is mostly based on weight with great interindividual variation in consumption. Suggested factors affecting propofol requirements include age, gender, ethnicity, anxiety, alcohol consumption, smoking, and concomitant valproate use. Genetic factors have not been widely explored. METHODS: We studied 1000 women undergoing breast cancer surgery under propofol and remifentanil anesthesia. Depth of anesthesia was monitored with State Entropy TM...

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism characterized by typical muscular symptoms, ranging from paresis to complete paralysis, commonly associated with low potassium blood levels (<3 mmol/l). It is more commonly reported in adult Asian individuals and can lead to life-threatening situations. Therefore, early clinical diagnosis and targeted therapy are of crucial importance. In this article, we report the case of a 17-year-old adolescent with a Vietnamese background and known Graves' disease who was admitted with typical TPP-related symptoms but no hypokalemia...