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Calcium channel subunit

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https://www.readbyqxmd.com/read/29694233/functional-features-of-the-finger-domain-of-deg-enac-channels-mec-4-and-unc-8
#1
Cristina Matthewman, Christina K Johnson, David M Miller Iii, Laura Bianchi
UNC-8 and MEC-4 are two members of the DEG/ENaC family of voltage-independent Na+ channels that share a high degree of sequence homology and functional similarity. For example, both can be hyperactivated by genetic mutations (UNC-8(d) and MEC-4(d)) that induce neuronal death by necrosis. Both depend in vivo on chaperone protein MEC-6 for function, as demonstrated by the finding that neuronal death induced by hyperactive UNC-8 and MEC-4 channels is prevented by null mutations in mec-6. UNC-8 and MEC-4 differ functionally in three major ways: 1) MEC-4 is calcium permeable whereas UNC-8 is not; 2) UNC-8, but not MEC-4, is blocked by extracellular calcium and magnesium in the micromolar range; 3) MEC-6 increases the number of MEC-4 channels at the cell surface in oocytes but does not have this effect on UNC-8...
April 25, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29692624/comparative-analysis-of-molecular-signatures-suggests-the-use-of-gabapentin-for-the-management-of-endometriosis-associated-pain
#2
Brice Bellessort, Anne Bachelot, Virginie Grouthier, Camille De Lombares, Nicolas Narboux-Neme, Paolo Garagnani, Chiara Pirazzini, Simonetta Astigiano, Luca Mastracci, Anastasia Fontaine, Gladys Alfama, Evelyne Duvernois-Berthet, Giovanni Levi
Background: It has been repetitively shown that the transcription factors DLX5 and DLX6 are drastically downregulated in endometriotic lesions when compared with eutopic endometrium. These findings suggest that regulatory cascades involving DLX5/6 might be at the origin of endometriosis symptoms such as chronic pelvic pain (CPP). We have shown that inactivation of Dlx5 and Dlx5/6 in the mouse uterus results in an endometrial phenotype reminiscent of endometriosis. Methods: We focused on genes that present a similar deregulation in endometriosis and in Dlx5/6 -null mice in search of new endometriosis targets...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29681531/calhm3-is-essential-for-rapid-ion-channel-mediated-purinergic-neurotransmission-of-gpcr-mediated-tastes
#3
Zhongming Ma, Akiyuki Taruno, Makoto Ohmoto, Masafumi Jyotaki, Jason C Lim, Hiroaki Miyazaki, Naomi Niisato, Yoshinori Marunaka, Robert J Lee, Henry Hoff, Riley Payne, Angelo Demuro, Ian Parker, Claire H Mitchell, Jorge Henao-Mejia, Jessica E Tanis, Ichiro Matsumoto, Michael G Tordoff, J Kevin Foskett
Binding of sweet, umami, and bitter tastants to G protein-coupled receptors (GPCRs) in apical membranes of type II taste bud cells (TBCs) triggers action potentials that activate a voltage-gated nonselective ion channel to release ATP to gustatory nerves mediating taste perception. Although calcium homeostasis modulator 1 (CALHM1) is necessary for ATP release, the molecular identification of the channel complex that provides the conductive ATP-release mechanism suitable for action potential-dependent neurotransmission remains to be determined...
April 13, 2018: Neuron
https://www.readbyqxmd.com/read/29675583/do-alcohol-related-ampa-type-glutamate-receptor-adaptations-promote-intake
#4
F Woodward Hopf, Regina A Mangieri
Ionotropic glutamate receptors (AMPA, NMDA, and kainate receptors) play a central role in excitatory glutamatergic signaling throughout the brain. As a result, functional changes, especially long-lasting forms of plasticity, have the potential to profoundly alter neuronal function and the expression of adaptive and pathological behaviors. Thus, alcohol-related adaptations in ionotropic glutamate receptors are of great interest, since they could promote excessive alcohol consumption, even after long-term abstinence...
April 20, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29656875/structural-mechanism-of-functional-modulation-by-gene-splicing-in-nmda-receptors
#5
Michael C Regan, Timothy Grant, Miranda J McDaniel, Erkan Karakas, Jing Zhang, Stephen F Traynelis, Nikolaus Grigorieff, Hiro Furukawa
Alternative gene splicing gives rise to N-methyl-D-aspartate (NMDA) receptor ion channels with defined functional properties and unique contributions to calcium signaling in a given chemical environment in the mammalian brain. Splice variants possessing the exon-5-encoded motif at the amino-terminal domain (ATD) of the GluN1 subunit are known to display robustly altered deactivation rates and pH sensitivity, but the underlying mechanism for this functional modification is largely unknown. Here, we show through cryoelectron microscopy (cryo-EM) that the presence of the exon 5 motif in GluN1 alters the local architecture of heterotetrameric GluN1-GluN2 NMDA receptors and creates contacts with the ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, which are absent in NMDA receptors lacking the exon 5 motif...
April 10, 2018: Neuron
https://www.readbyqxmd.com/read/29644895/%C3%AE-1-subunit-of-the-calcium-sensitive-potassium-channel-modulates-the-pulmonary-vascular-smooth-muscle-cell-response-to-hypoxia
#6
Elizabeth A Barnes, Lori Lee, Shayna L Barnes, Robert Brenner, Cristina M Alvira, David N Cornfield
Accessory subunits associated with the calcium-sensitive potassium channel (BKCa ), a major determinant of vascular tone, confer functional and anatomical diversity. The β1 subunit increases Ca2+ -, and voltage-sensitivity of the BKCa channel and is expressed exclusively in smooth muscle cells (SMC). Evidence supporting the physiologic significance of the β1 subunit includes the observations that murine models with deletion of the β1 subunit are hypertensive and that humans with a gain-of-function β1 mutation are at decreased risk of diastolic hypertension, However, whether the β1 subunit of the BKCa channel contributes to the low tone that characterizes the normal pulmonary circulation or modulates the pulmonary vascular response to hypoxia remains unknown...
April 12, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29627324/from-excitation-to-intracellular-ca-2-movements-in-skeletal-muscle-basic-aspects-and-related-clinical-disorders
#7
REVIEW
Bruno Allard
In skeletal muscle fiber, excitation-contraction coupling corresponds to the sequence of events occurring from action potential firing to initiation of contraction by an increase in cytosolic Ca2+ . These events are elicited in response to excitation of the motor neuron which induces trains of action potentials in the muscle cell that spread along the sarcolemma and in depth along the T-tubule membrane. Depolarization of the T-tubule membrane induces a conformational change in a protein complex, called the dihydropyridine receptor, which opens a calcium channel anchored in the membrane of the sarcoplasmic reticulum, called the ryanodine receptor, in charge of release of Ca2+ ions that activate contractile proteins...
March 9, 2018: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/29618985/the-complex-role-of-store-operated-calcium-entry-pathways-and-related-proteins-in-the-function-of-cardiac-skeletal-and-vascular-smooth-muscle-cells
#8
REVIEW
Javier Avila-Medina, Isabel Mayoral-Gonzalez, Alejandro Dominguez-Rodriguez, Isabel Gallardo-Castillo, Juan Ribas, Antonio Ordoñez, Juan A Rosado, Tarik Smani
Cardiac, skeletal, and smooth muscle cells shared the common feature of contraction in response to different stimuli. Agonist-induced muscle's contraction is triggered by a cytosolic free Ca2+ concentration increase due to a rapid Ca2+ release from intracellular stores and a transmembrane Ca2+ influx, mainly through L-type Ca2+ channels. Compelling evidences have demonstrated that Ca2+ might also enter through other cationic channels such as Store-Operated Ca2+ Channels (SOCCs), involved in several physiological functions and pathological conditions...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29605472/interactive-effects-of-salinity-and-temperature-acclimation-on-gill-morphology-and-gene-expression-in-threespine-stickleback
#9
Taylor C Gibbons, Tara L McBryan, Patricia M Schulte
Colonization of freshwater habitats from marine environments exposes organisms to novel combinations of temperature and salinity, but little is known about physiological responses to the interactive effects of these stressors. Here, we examined the effects of temperature (14 versus 4 °C) and salinity (11 versus 0.3 ppt) on gill gene expression in marine, anadromous, and freshwater populations of threespine stickleback (Gasterosteus aculeatus). Expression of the epithelial calcium channel was not affected by temperature or salinity, but had significantly higher expression in the freshwater ecotype...
March 29, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29589117/the-degenerin-region-of-the-human-bile-acid-sensitive-ion-channel-basic-is-involved-in-channel-inhibition-by-calcium-and-activation-by-bile-acids
#10
Alexandr V Ilyaskin, Sonja A Kirsch, Rainer A Böckmann, Heinrich Sticht, Christoph Korbmacher, Silke Haerteis, Alexei Diakov
The bile acid-sensitive ion channel (BASIC) is a member of the ENaC/degenerin family of ion channels. It is activated by bile acids and inhibited by extracellular Ca2+ . The aim of this study was to explore the molecular mechanisms mediating these effects. The modulation of BASIC function by extracellular Ca2+ and tauro-deoxycholic acid (t-DCA) was studied in Xenopus laevis oocytes heterologously expressing human BASIC using the two-electrode voltage-clamp and outside-out patch-clamp techniques. Substitution of aspartate D444 to alanine or cysteine in the degenerin region of BASIC, a region known to be critically involved in channel gating, resulted in a substantial reduction of BASIC Ca2+ sensitivity...
March 27, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29580153/peripheral-nerve-injury-increases-contribution-of-l-type-calcium-channels-to-synaptic-transmission-in-spinal-lamina-ii-role-of-%C3%AE-2%C3%AE-1-subunits
#11
Sascha Ra Alles, Esperanza Garcia, Sridhar Balasubramanyan, Karen Jones, John R Tyson, Twinkle Joy, Terrance P Snutch, Peter A Smith
Background Following peripheral nerve chronic constriction injury, the accumulation of the α2δ-1 auxiliary subunit of voltage-gated Ca2+ channels in primary afferent terminals contributes to the onset of neuropathic pain. Overexpression of α2δ-1 in Xenopus oocytes increases the opening properties of Cav 1.2 L-type channels and allows Ca2+ influx at physiological membrane potentials. We therefore posited that L-type channels play a role in neurotransmitter release in the superficial dorsal horn in the chronic constriction injury model of neuropathic pain...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29568937/genetic-analysis-of-sick-sinus-syndrome-in-a-family-harboring-compound-cacna1c-and-ttn-mutations
#12
Yao-Bin Zhu, Jie-Wei Luo, Fen Jiang, Gui Liu
Sick sinus syndrome (SSS) is a sinus node dysfunction characterized by severe sinus bradycardia. SSS results in insufficient blood supply to the brain, heart, kidneys, and other organs and is associated with the increased risk of sudden cardiac death. Bradyarrhythmia appears in the absence of any associated cardiac pathology and displays a genetic legacy. The present study identified a family with primary manifestation of sinus bradycardia (five individuals) along with early repolarization (four individuals) and atrial fibrillation (one individual)...
March 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29563324/binding-characteristics-and-analgesic-effects-of-mirogabalin-a-novel-ligand-for-the-%C3%AE-2-%C3%AE-subunit-of-voltage-gated-calcium-channels
#13
Yuki Domon, Naohisa Arakawa, Tatsuya Inoue, Fumihiko Matsuda, Makoto Takahashi, Naotoshi Yamamura, Kiyonori Kai, Yutaka Kitano
Mirogabalin ([(1 R ,5 S ,6 S )-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid), a novel ligand for the α2 δ subunit of voltage-gated calcium channels, is being developed to treat pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. In the present study, we investigated the in vitro binding characteristics and in vivo analgesic effects of mirogabalin, compared to those of pregabalin, a standard α2 δ ligand. Mirogabalin showed potent and selective binding affinities for the α2 δ subunits, while having no effects on 186 off-target proteins...
March 21, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29558628/differential-participation-of-calcium-activated-potassium-channel-in-endothelium-dependent-hyperpolarization-type-relaxation-in-superior-mesenteric-arteries-of-spontaneously-hypertensive-rats
#14
Makoto Ando, Takayuki Matsumoto, Shota Kobayashi, Maika Iguchi, Kumiko Taguchi, Tsuneo Kobayashi
The purpose of this study was to determine the relationship of KCa channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29556214/calcium-channels-in-postnatal-development-of-rat-pancreatic-beta-cells-and-their-role-in-insulin-secretion
#15
Neivys García-Delgado, Myrian Velasco, Carmen Sánchez-Soto, Carlos Manlio Díaz-García, Marcia Hiriart
Pancreatic beta cells during the first month of development acquire functional maturity, allowing them to respond to variations in extracellular glucose concentration by secreting insulin. Changes in ionic channel activity are important for this maturation. Within the voltage-gated calcium channels (VGCC), the most studied channels are high-voltage-activated (HVA), principally L-type; while low-voltage-activated (LVA) channels have been poorly studied in native beta cells. We analyzed the changes in the expression and activity of VGCC during the postnatal development in rat beta cells...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29552611/data-on-solubilization-identification-and-thermal-stability-of-human-presenilin-2
#16
Ge Yang, Kun Yu, Jan Kubicek, Jörg Labahn
The data presented here are related to the research article entitled "Expression, purification, and preliminary characterization of human presenilin-2" [1]. Human Presenilin-2 is the catalytic subunit of γ-secretase and a possible calcium leakage channel (Kimberly et al., 2000; Tu et al., 2006) [2], [3]. HisPS2 which was obtained by overexpression in E. coli strain C43 (DE3) was extracted by detergent solubilisation. The sample isolation efficiency by detergents and the protein identification by mass spectrometry and western blot are described...
April 2018: Data in Brief
https://www.readbyqxmd.com/read/29545968/calcium-channel-%C3%AE-2%C3%AE-1-subunit-as-a-novel-biomarker-for-diagnosis-of-hepatocellular-carcinoma
#17
Sana Amhimmid Badr, Maryan Waheeb Fahmi, Manal Mahmoud Nomir, Mamdouh Mohammad El-Shishtawy
Objective: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. The identification of new simple, inexpensive and highly accurate markers for HCC diagnosis and screening is needed. This case-control study evaluates the role of annexin A2 and voltage-gated calcium channels α2δ1 subunit as serum biomarkers for HCC diagnosis. Methods: The study comprised three groups: group 1, 50 patients with an initial diagnosis of HCC associated with chronic hepatitis C virus infection; group 2, 25 patients diagnosed with chronic hepatitis C virus infection and cirrhosis without any evidence of HCC; and group 3, 15 healthy controls...
February 2018: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/29545262/downregulation-of-l-type-voltage-gated-ca-2-voltage-gated-k-and-large-conductance-ca-2-activated-k-channels-in-vascular-myocytes-from-salt-loading-offspring-rats-exposed-to-prenatal-hypoxia
#18
Bailin Liu, Ruixiu Shi, Xiang Li, Yanping Liu, Xueqin Feng, Xueyi Chen, Xiaorong Fan, Yingying Zhang, Wenna Zhang, Jiaqi Tang, Xiuwen Zhou, Na Li, Xiyuan Lu, Zhice Xu
BACKGROUND: Prenatal hypoxia is suggested to be associated with increased risks of hypertension in offspring. This study tested whether prenatal hypoxia resulted in salt-sensitive offspring and its related mechanisms of vascular ion channel remodeling. METHODS AND RESULTS: Pregnant rats were housed in a normoxic (21% O2 ) or hypoxic (10.5% O2 ) chamber from gestation days 5 to 21. A subset of male offspring received a high-salt diet (8% NaCl) from 4 to 12 weeks after birth...
March 15, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29545233/expanding-the-phenotype-of-homozygous-kcnma1-mutations-dyskinesia-epilepsy-intellectual-disability-cerebellar-and-corticospinal-tract-atrophy
#19
Gözde Yeşil, Ayşe Aralaşmak, Enes Akyüz, Dilara İçağasıoğlu, Türkan Uygur Şahin, Yavuz Bayram
BACKGROUND: The KCNMA1 gene encodes the α-subunit of the large conductance, voltage and calcium-sensitive potassium channel (BK channels) which plays an important role in neuronal excitability. Heterozygous mutations in KCNMA1 were firstly described in a large family with generalized epilepsy and paroxysmal nonkinesigenic dyskinesia. Recently, homozygous KCNMA1 mutations were reported to cause a phenotype of cerebellar atrophy, developmental delay and seizures. CASE REPORT: Herein; we report a patient with a novel homozygous truncating mutation in KCNMA1 (p...
March 16, 2018: Balkan Medical Journal
https://www.readbyqxmd.com/read/29534490/atp-release-channels
#20
REVIEW
Akiyuki Taruno
Adenosine triphosphate (ATP) has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels...
March 11, 2018: International Journal of Molecular Sciences
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