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https://www.readbyqxmd.com/read/29932499/inhibition-of-bk-ca-negatively-alters-cardiovascular-function
#1
Nishi H Patel, Justin Johannesen, Kajol Shah, Sumanta K Goswami, Neel J Patel, Devasena Ponnalagu, Andrew R Kohut, Harpreet Singh
Large conductance calcium and voltage-activated potassium channels (BKC a ) are transmembrane proteins, ubiquitously expressed in the majority of organs, and play an active role in regulating cellular physiology. In the heart, BKC a channels are known to play a role in regulating the heart rate and protect it from ischemia-reperfusion injury. In vascular smooth muscle cells, the opening of BKC a channels results in membrane hyperpolarization which eventually results in vasodilation mediated by a reduction in Ca2+ influx due to the closure of voltage-dependent Ca2+ channels...
June 2018: Physiological Reports
https://www.readbyqxmd.com/read/29930980/molecular-basis-and-differentiation-associated-alterations-of-anion-secretion-in-human-duodenal-enteroid-monolayers
#2
Jianyi Yin, Chung-Ming Tse, Leela Rani Avula, Varsha Singh, Jennifer Foulke-Abel, Hugo R de Jonge, Mark Donowitz
Background & Aims: Human enteroids present a novel tool to study human intestinal ion transport physiology and pathophysiology. The present study describes the contributions of Cl- and HCO3 - secretion to total cyclic adenosine monophosphate (cAMP)-stimulated electrogenic anion secretion in human duodenal enteroid monolayers and the relevant changes after differentiation. Methods: Human duodenal enteroids derived from 4 donors were grown as monolayers and differentiated by a protocol that includes the removal of Wnt3A, R-spondin1, and SB202190 for 5 days...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29930145/the-transcription-factor-etv1-induces-atrial-remodeling-and-arrhythmia
#3
Carolin Rommel, Stephan Rösner, Achim Lother, Margareta Barg, Martin Schwaderer, Ralf Gilsbach, Timo Bömicke, Tilman Schnick, Sandra Mayer, Sophia Doll, Michael Hesse, Oliver Kretz, Brigitte Stiller, Franz-Josef Neumann, Matthias Mann, Markus Krane, Bernd K Fleischmann, Ursula Ravens, Lutz Hein
<u>Rationale:</u> Structural and electrophysiological remodeling of the atria are recognized consequences of sustained atrial arrhythmias, such as atrial fibrillation (AF). The identification of underlying key molecules and signaling pathways has been challenging due to the changing cell type composition during structural remodeling of the atria. <u>Objective:</u> Thus, the aims of our study were (1) to search for transcription factors and downstream target genes, which are involved in atrial structural remodeling, (2) to characterize the significance of the transcription factor ETV1 in atrial remodeling and arrhythmia and (3) to identify ETV1-dependent gene regulatory networks in atrial cardiac myocytes...
June 21, 2018: Circulation Research
https://www.readbyqxmd.com/read/29929098/kcnj6-girk2-trisomy-is-not-sufficient-for-conferring-the-susceptibility-to-infantile-spasms-seen-in-the-ts65dn-mouse-model-of-down-syndrome
#4
Krutika Joshi, Lily Shen, Feng Cao, Susan Dong, Zhengping Jia, Miguel A Cortez, O Carter Snead
OBJECTIVE: Infantile spasms (IS) is a catastrophic childhood seizure disorder that is characterized by extensor and/or flexor spasms, cognitive deterioration and a characteristic EEG abnormality. The latter consists of a pattern of a spike-wave followed by an electrodecremental response (EDR), which is a flattening of the EEG waveform amplitude. The mechanism/circuitry that underpins IS is unknown. Children with Down Syndrome (DS) are particularly vulnerable to IS. The standard mouse model of DS is the Ts65Dn mutant mouse (Ts)...
June 12, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29928032/activation-of-trek-currents-by-riluzole-in-three-subgroups-of-cultured-mouse-nodose-ganglion-neurons
#5
Diego Fernández-Fernández, Alba Cadaveira-Mosquera, Lola Rueda-Ruzafa, Salvador Herrera-Pérez, Emma L Veale, Antonio Reboreda, Alistair Mathie, J Antonio Lamas
Two-pore domain potassium channels (K2P) constitute major candidates for the regulation of background potassium currents in mammalian cells. Channels of the TREK subfamily are also well positioned to play an important role in sensory transduction due to their sensitivity to a large number of physiological and physical stimuli (pH, mechanical, temperature). Following our previous report describing the molecular expression of different K2P channels in the vagal sensory system, here we confirm that TREK channels are functionally expressed in neurons from the mouse nodose ganglion (mNG)...
2018: PloS One
https://www.readbyqxmd.com/read/29925780/mouse-%C3%AE-defensin-3-a-defensin-inhibitor-of-both-its-endogenous-and-exogenous-potassium-channels
#6
Yaoyun Zhang, Yonghui Zhao, Hongyue Liu, Weiwei Yu, Fan Yang, Wenhua Li, Zhijian Cao, Yingliang Wu
The human defensins are recently discovered to inhibit potassium channels, which are classical targets of the animal toxins. Whether other vertebrate defensins are potassium channel inhibitors remains unknown. In this work, we reported that the mouse &beta;-defensin 3 (mBD3) was a novel inhibitor of both endogenous and exogenous potassium channels. The structural analysis showed that mBD3 is the most identical to human Kv1.3 channel-sensitive human &beta;-defensin 2 (hBD2). However, the pharmacological profiles indicated that the recombinant mBD3 (rmBD3) weakly inhibited the mouse and human Kv1...
June 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29924635/extracellular-loop-of-auxiliary-%C3%AE-1-subunit-is-involved-in-the-regulation-of-bk-ca-channel-mechanosensitivity
#7
Fang Xin, Yuan Cheng, Jie Ren, Sitao Zhang, Ping Liu, Haiyan Zhao, Haixia Huang, Wei Wang
The large conductance Ca2+ -activated potassium (BKCa ) channel is activated by stretch. The stress regulated exon (STREX) in α subunits is known to affect mechanosensitivity of BKCa channels. However, in human colonic smooth muscle cells (HCoSMCs) we found that the α subunits without STREX (ZERO-BK) and β1 subunits could be detected yet the cells were mechanosensitive. Whether the β1 subunit is involved in the regulation of BKCa mechanosensitivity is unclear. In the present study, ZERO-BK and β1 subunits were individually expressed or coexpressed in HEK293 cells and cell-attached patch-clamp techniques were used to measure BKCa currents defining mechanosensitivity...
June 20, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29922947/comparative-effects-of-calcium-and-potassium-channel-modulators-on-ischemia-reperfusion-injury-in-the-isolated-rat-heart
#8
Nina Simonovic, Vladimir Jakovljevic, Jovana Jeremic, Zarko Finderle, Ivan Srejovic, Tamara Nikolic Turnic, Isidora Milosavljevic, Vladimir Zivkovic
The aim of this study was to examine and compare the effects of the acute administration of verapamil or amlodipine as representatives of the calcium channel blockers or nicorandil as a representative of the mitochondrial ATP-dependent potassium (KATP ) channel opener to cardiac contractility, coronary flow, and oxidative stress markers on ischemia/reperfusion injury in the isolated rat heart. The hearts of adult male Wistar albino rats (n = 60 total, 12 per group) were divided into five groups, two controls (preconditioning with Krebs-Henseleit solution) and three experimental depending on acute administrated pharmacological agents (0,63 µmol/L of verapamil, 0,1 µmol/L of amlodipine, and 200 µmol/L of nicorandil)...
June 19, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29922167/inhibition-of-small-conductance-calcium-activated-potassium-sk-channels-prevents-arrhythmias-in-rat-atria-during-%C3%AE-adrenergic-and-muscarinic-receptor-activation
#9
Lasse Skibsbye, Anne K Bengaard, A M Uldum-Nielsen, Kim Boddum, Torsten Christ, Thomas Jespersen
Sympathetic and vagal activation is linked to atrial arrhythmogenesis. Here we investigated the small conductance Ca2+ -activated K+ (SK)-channel pore-blocker N -(pyridin-2-yl)-4-(pyridine-2-yl)thiazol-2-amine (ICA) on action potential (AP) and atrial fibrillation (AF) parameters in isolated rat atria during β-adrenergic [isoprenaline (ISO)] and muscarinic M2 [carbachol (CCh)] activation. Furthermore, antiarrhythmic efficacy of ICA was benchmarked toward the class-IC antiarrhythmic drug flecainide (Fleca)...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29916016/rna-editing-deficiency-in-neurodegeneration
#10
Ileana Lorenzini, Stephen Moore, Rita Sattler
The molecular process of RNA editing allows changes in RNA transcripts that increase genomic diversity. These highly conserved RNA editing events are catalyzed by a group of enzymes known as adenosine deaminases acting on double-stranded RNA (ADARs). ADARs are necessary for normal development, they bind to over thousands of genes, impact millions of editing sites, and target critical components of the central nervous system (CNS) such as glutamate receptors, serotonin receptors, and potassium channels. Dysfunctional ADARs are known to cause alterations in CNS protein products and therefore play a role in chronic or acute neurodegenerative and psychiatric diseases as well as CNS cancer...
2018: Advances in Neurobiology
https://www.readbyqxmd.com/read/29915289/kcnn4-is-a-modifier-gene-of-intestinal-cystic-fibrosis-preventing-lethality-in-the-cftr-f508del-mouse
#11
Amber R Philp, Texia T Riquelme, Pamela Millar-Büchner, Rodrigo González, Francisco V Sepúlveda, L Pablo Cid, Carlos A Flores
Nearly 70% of cystic fibrosis (CF) patients bear the phenylalanine-508 deletion but disease severity differs greatly, and is not explained by the existence of different mutations in compound heterozygous. Studies demonstrated that genes other than CFTR relate to intestinal disease in humans and CF-mouse. Kcnn4, the gene encoding the calcium-activated potassium channel KCa 3.1, important for intestinal secretion, is present in a locus linked with occurrence of intestinal CF-disease in mice and humans. We reasoned that it might be a CF-modifier gene and bred a CF-mouse with Kcnn4 silencing, finding that lethality was almost abolished...
June 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29915142/impaired-%C3%AE-cell-glucokinase-as-an-underlying-mechanism-in-diet-induced-diabetes
#12
Brian Lu, Kiran Kurmi, Miguel Munoz-Gomez, Egon J Jacobus Ambuludi, Jason M Tonne, Kuntol Rakshit, Taro Hitosugi, Yogish C Kudva, Aleksey V Matveyenko, Yasuhiro Ikeda
High-fat diet (HFD)-fed mouse models have been widely used to study early type 2 diabetes. Decreased β-cell glucokinase (GCK) expression has been observed in HFD-induced diabetes. However, owing to its crucial roles in glucose metabolism in the liver and in islet β-cells, the contribution of decreased GCK expression to the development of HFD-induced diabetes is unclear. Here, we employed a β-cell-targeted gene transfer vector and determined the impact of β-cell-specific increase in GCK expression on β-cell function and glucose handling in vitro and in vivo Overexpression of GCK enhanced glycolytic flux, ATP-sensitive potassium channel activation and membrane depolarization, and increased proliferation in Min6 cells...
June 13, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29915136/constitutive-and-synaptic-activation-of-girk-channels-differentiates-mature-and-newborn-dentate-granule-cells
#13
Jose Carlos Gonzalez, S Alisha Epps, Sean J Markwardt, Jacques I Wadiche, Linda Overstreet-Wadiche
Sparse neural activity in the dentate gyrus (DG) is enforced by powerful networks of inhibitory GABAergic interneurons in combination with low intrinsic excitability of the principal neurons, the dentate granule cells (GCs). Although the cellular and circuit properties that dictate synaptic inhibition are well studied, less is known about mechanisms that confer low GC intrinsic excitability. Here we demonstrate that intact G-protein mediated signaling contributes to the characteristic low resting membrane potential that differentiates mature dentate GCs from CA1 pyramidal cells and developing adult-born GCs...
June 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29913708/ionic-mechanisms-of-post-spike-excitability-changes-during-high-frequency-firing-rates
#14
Erik A Fransén, Peter J Ahlström
Aims Axonal hyperexcitability in peripheral nerves has been observed in patients with neuropathic pain [1]. The use-dependent propagation of double pulses, recovery cycles, was found to be different in patients relative to healthy controls. Methods We study the mechanisms underlying the recovery cycle phenomenon using a biophysical model of a C-fiber [2]. The model represents the spatial extent of the axon including its passive properties as well as ion channels of Hodgkin-Huxley type. In vitro voltage clamp recordings from dissociated small DRG somata from rat were performed to assess model predictions...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29912156/vasodilator-activity-of-compounds-isolated-from-plants-used-in-mexican-traditional-medicine
#15
Francisco J Luna-Vázquez, César Ibarra-Alvarado, María Del Rayo Camacho-Corona, Alejandra Rojas-Molina, J Isela Rojas-Molina, Abraham García, Moustapha Bah
Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso -dihydroguaiaretic acid [half maximal effective concentration (EC50 ), 49...
June 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29908238/small-conductance-calcium-activated-potassium-sk-channel-dependent-and-independent-effects-of-riluzole-on-neuropathic-pain-related-amygdala-activity-and-behaviors-in-rats
#16
Jeremy M Thompson, Vadim Yakhnitsa, Guangchen Ji, Volker Neugebauer
BACKGROUND AND PURPOSE: Chronic neuropathic pain is an important healthcare issue with significant emotional components. The amygdala is a brain region involved in pain and emotional-affective states and disorders. The central amygdala output nucleus (CeA) contains small-conductance calcium-activated potassium (SK) channels that can control neuronal activity. A clinically available therapeutic, riluzole can activate SK channels and may have antinociceptive effects through a supraspinal action...
June 13, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29907571/synonymous-nucleotide-modification-of-the-kcnh2-gene-affects-both-mrna-characteristics-and-translation-of-the-encoded-herg-ion-channel
#17
Alexander C Bertalovitz, Marika L Osterbur Badhey, Thomas V McDonald
Synonymous nucleotide variation is increasingly recognized as a factor than can affect protein expression, but the underlying mechanisms are incompletely understood. Here, we investigated whether synonymous changes could affect expression of the potassium voltage gated channel subfamily H member 2 (KCNH2) gene, encoding the human ether-a-go-go related gene (hERG) ion channel which is linked to hereditary cardiac arrhythmia. We examined a previously described synthetic version (hERG-CM) with synonymous substitutions designed to reduce GC content, rare codons, and mRNA secondary structure relative to the native construct (hERG-NT)...
June 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29907477/successful-treatment-of-normokalemic-periodic-paralysis-with-hydrochlorothiazide
#18
Yuichi Akaba, Satoru Takahashi, Yoshiaki Sasaki, Hiroki Kajino
BACKGROUND: Periodic paralysis (PP) is an autosomal dominant muscle disorder characterized by periodic muscle weakness attacks associated with serum potassium level variations. It is classified into hypokalemic (hypoKPP), hyperkalemic (hyperKPP), and normokalemic (normoKPP) forms based on the ictal serum potassium level. HyperKPP and normoKPP are caused by mutations of the same gene SCN4A, the gene encoding the skeletal muscle voltage-gated sodium channel. Prophylactic treatment with thiazide diuretics is highly effective in preventing attacks in hyperKPP...
June 12, 2018: Brain & Development
https://www.readbyqxmd.com/read/29907377/neurotropin-inhibits-neuronal-activity-through-potentiation-of-sustained-k-v-currents-in-primary-cultured-drg-neurons
#19
Hiroyuki Kawai, Nozomi Asaoka, Takahito Miyake, Kazuki Nagayasu, Takayuki Nakagawa, Hisashi Shirakawa, Shuji Kaneko
Neurotropin (NTP) is a Japanese analgesic agent for treating neuropathic pain; however, its method of action remains unclear. This study examined the effects of NTP on the activity of small dorsal root ganglion (DRG) neurons using whole-cell patch clamp recordings. After 3 days of treatment, NTP decreased current injection-induced firing activity of cultured DRG neurons by raising the current threshold for action potential generation. Additionally, NTP increased the sustained component of voltage-gated potassium (Kv ) channel currents without affecting other K+ currents...
May 31, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29907035/strontium-and-barium-in-aqueous-solution-and-a-potassium-channel-binding-site
#20
Mangesh I Chaudhari, Susan B Rempe
Ion hydration structure and free energy establish criteria for understanding selective ion binding in potassium (K+ ) ion channels and may be significant to understanding blocking mechanisms as well. Recently, we investigated the hydration properties of Ba2+ , the most potent blocker of K+ channels among the simple metal ions. Here, we use a similar method of combining ab initio molecular dynamics simulations, statistical mechanical theory, and electronic structure calculations to probe the fundamental hydration properties of Sr2+ , which does not block bacterial K+ channels...
June 14, 2018: Journal of Chemical Physics
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