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Calcium channel subunit

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https://www.readbyqxmd.com/read/29044210/calmodulin-confers-calcium-sensitivity-to-the-stability-of-the-distal-intracellular-assembly-domain-of-kv7-2-channels
#1
Alessandro Alaimo, Eider Nuñez, Paloma Aivar, Juncal Fernández-Orth, Carolina Gomis-Perez, Ganeko Bernardo-Seisdedos, Covadonga Malo, Alvaro Villarroel
Tetrameric coiled-coil structures are present in many ion channels, often adjacent to a calmodulin (CaM) binding site, although the relationship between the two is not completely understood. Here we examine the dynamic properties of the ABCD domain located in the intracellular C-terminus of tetrameric, voltage-dependent, potassium selective Kv7.2 channels. This domain encompasses the CaM binding site formed by helices A and B, followed by helix C, which is linked to the helix D coiled-coil. The data reveals that helix D stabilizes CaM binding, promoting trans-binding (CaM embracing neighboring subunits), and they suggest that the ABCD domain can be exchanged between subunits of the tetramer...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042943/suxiao-jiuxin-pill-protects-cardiomyocytes-against-mitochondrial-injury-and-alters-gene-expression-during-ischemic-injury
#2
Xiaofen Ruan, Tiejun Chen, Xiaolong Wang, Yiping Li
Suxiao Jiuxin Pill (SX), a traditional Chinese medicine compound consisting primarily of tetramethylpyrazine and borneol, has been reported to protect against ischemic heart disease. However, the effects of SX on mitochondrial injury and gene expression in various signaling pathways are unclear. The aim of the present study was to investigate the effects of SX on mitochondrial injury and to screen the expression of genes potentially altered by SX using a cell culture model of ischemic injury. Simulated ischemia was established by culturing HL-1 cardiomyocytes in Dulbecco's modified Eagle medium without glucose or serum in a hypoxic chamber containing 95% N2 and 5% CO2 for 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042318/mechanisms-of-%C3%AE-opioid-receptor-inhibition-of-nmda-receptor-induced-substance-p-release-in-the-rat-spinal-cord
#3
Wenling Chen, Helena S Ennes, James A McRoberts, Juan Carlos Marvizon
The interaction between NMDA receptors and μ-opioid receptors in primary afferent terminals was studied by using NMDA to induce substance P release, measured as neurokinin 1 receptor internalization. In rat spinal cord slices, the μ-opioid receptor agonists morphine, DAMGO and endomorphin-2 inhibited NMDA-induced substance P release, whereas the antagonist CTAP right-shifted the concentration response of DAMGO. In vivo, substance P release induced by intrathecal NMDA after priming with BDNF was inhibited by DAMGO...
October 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29038230/ghrelin-receptor-constitutive-activity-reduces-surface-expression-of-voltage-gated-calcium-channels-in-a-cav%C3%AE-dependent-manner
#4
Emilio R Mustafá, Eduardo J López Soto, Valentina Martínez Damonte, Silvia S Rodríguez, Diane Lipscombe, Jesica Raingo
Voltage gated calcium (CaV) channels couple membrane depolarization to calcium influx, triggering a range of calcium-dependent cellular processes. CaV channels are therefore critical in shaping neuronal activity and function, depending on their individual temporal and spatial properties. Furthermore, many neurotransmitters and drugs that act through G protein coupled receptors (GPCRs), modulate neuronal activity by altering the expression, trafficking, or function of CaV channels. GPCR-dependent mechanisms that down regulate CaV channel expression levels are observed in many neurons but are, by comparison, less studied...
October 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29023772/negative-modulation-of-the-gabaa-%C3%AF-1-receptor-function-by-l-cysteine
#5
Andrea N Beltrán González, Florencia Vicentini, Daniel J Calvo
L-Cysteine is an endogenous Sulphur containing amino acid with multiple and varied roles in the central nervous system, including neuroprotection and the maintenance of the redox balance. However, it was also suggested as an excitotoxic agent implicated in the pathogenesis of neurological disorders such as Parkinson's and Alzheimer's disease. L-Cysteine can modulate the activity of ionic channels, including voltage-gated calcium channels and glutamatergic NMDA receptors, whereas its effects on GABAergic neurotransmission had not been studied before...
October 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29021340/downregulation-of-the-wnt-%C3%AE-catenin-signaling-pathway-by-cacnb4
#6
Mohamad Rima, Marwa Daghsni, Anaïs Lopez, Ziad Fajloun, Lydie Lefrancois, Mireia Dunach, Yasuo Mori, Philippe Merle, Juan L Brusés, Michel de Waard, Michel Ronjat
The β4 isoform of the β-subunits of Voltage-Gated Calcium Channel regulates cell proliferation and cell cycle progression. Herein we show that co-expression of the β4-subunit with actors of the canonical Wnt/β-catenin signaling pathway in a hepatoma cell line inhibits Wnt responsive gene transcription and decreases cell division, in agreement with the role of the Wnt pathway in cell proliferation. β4-subunit-mediated inhibition of Wnt signaling is observed in the presence of LiCl, an inhibitor of GSK3 that promotes β-catenin translocation to the nucleus...
October 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29019983/human-trpml1-channel-structures-in-open-and-closed-conformations
#7
Philip Schmiege, Michael Fine, Günter Blobel, Xiaochun Li
Transient receptor potential mucolipin 1 (TRPML1) is a Ca(2+)-releasing cation channel that mediates the calcium signalling and homeostasis of lysosomes. Mutations in TRPML1 lead to mucolipidosis type IV, a severe lysosomal storage disorder. Here we report two electron cryo-microscopy structures of full-length human TRPML1: a 3.72-Å apo structure at pH 7.0 in the closed state, and a 3.49-Å agonist-bound structure at pH 6.0 in an open state. Several aromatic and hydrophobic residues in pore helix 1, helices S5 and S6, and helix S6 of a neighbouring subunit, form a hydrophobic cavity to house the agonist, suggesting a distinct agonist-binding site from that found in TRPV1, a TRP channel from a different subfamily...
October 11, 2017: Nature
https://www.readbyqxmd.com/read/28993142/ghrelin-upregulates-the-phosphorylation-of-the-glun2b-subunit-of-the-nmda-receptor-by-activating-ghsr1a-and-fyn-in-the-rat-hippocampus
#8
Liza Berrout, Masako Isokawa
Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity...
October 6, 2017: Brain Research
https://www.readbyqxmd.com/read/28986220/two-mutations-in-mitochondrial-atp6-gene-of-atp-synthase-related-to-human-cancer-affect-ros-calcium-homeostasis-and-mitochondrial-permeability-transition-in-yeast
#9
Katarzyna Niedzwiecka, Renata Tisi, Sara Penna, Malgorzata Lichocka, Danuta Plochocka, Roza Kucharczyk
The relevance of mitochondrial DNA (mtDNA) mutations in cancer process is still unknown. Since the mutagenesis of mitochondrial genome in mammals is not possible yet, we have exploited budding yeast S. cerevisiae as a model to study the effects of tumor-associated mutations in the mitochondrial MTATP6 gene, encoding subunit 6 of ATP synthase, on the energy metabolism. We previously reported that four mutations in this gene have a limited impact on the production of cellular energy. Here we show that two mutations, Atp6-P163S and Atp6-K90E (human MTATP6-P136S and MTATP6-K64E, found in prostate and thyroid cancer samples, respectively), increase sensitivity of yeast cells both to compounds inducing oxidative stress and to high concentrations of calcium ions in the medium, when Om45p, the component of porin complex in outer mitochondrial membrane (OM), was fused to GFP...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28975890/identification-and-validation-of-novel-prognostic-markers-in-renal-cell-carcinoma
#10
Maj Rabjerg
Kidney cancer (Renal Cell Carcinoma (RCC)) is one of the most deadly malignancies due to frequent late diagnosis and poor treatment options. Histologically, RCC embraces a wide variety of different subtypes with the clear cell variant (ccRCC) being the most common, accounting for 75-90% of all RCCs. At present, the surveillance protocols for follow-up of RCC patients after radical nephrectomy are based on the American Joint Committee on Cancers (AJCC) pathological tumor-node-metastasis (TNM) classification system...
October 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28974111/in-vitro-neurotoxicity-by-ropivacaine-is-reduced-by-silencing-cav3-3-t-type-calcium-subunits-in-neonatal-rat-sensory-neurons
#11
Xianjie Wen, Hua Liang, Heng Li, Weiming Ou, Han-Bing Wang, Hongzhen Liu, Shijie Li
Neurotoxicity of local anaesthetics has been alerted by more and more peoples. Cav3.1 and Cav3.2 T-type calcium channels were closely related with local anaesthetics toxicity. However, the role of Cav3.3, another subtype of the T-type calcium channel, on the neurotoxicity induced by local anaesthetics remains unclear. CaMKIIγ is a kind of multifunctional kinase and associated with a variety of physiological and pathological process. T-type calcium channel is closely related with CaMKIIγ. Up-regulation CaMKIIγ can increase T-type currents at the dorsal root ganglia (DRG)...
October 3, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28953901/allosteric-activation-mechanism-of-bk-channel-gating-ring-triggered-by-calcium-ions
#12
Ronghua Guan, Hui Zhou, Junwei Li, Shaoying Xiao, Chunli Pang, Yafei Chen, Xiangrong Du, Shaoxi Ke, Qiongyao Tang, Jiguo Su, Yong Zhan, Hailong An
Calcium ions bind at the gating ring which triggers the gating of BK channels. However, the allosteric mechanism by which Ca2+ regulates the gating of BK channels remains obscure. Here, we applied Molecular Dynamics (MD) and Targeted MD to the integrated gating ring of BK channels, and achieved the transition from the closed state to a half-open state. Our date show that the distances of the diagonal subunits increase from 41.0 Å at closed state to 45.7Å or 46.4 Å at a half-open state. It is the rotatory motion and flower-opening like motion of the gating rings which are thought to pull the bundle crossing gate to open ultimately...
2017: PloS One
https://www.readbyqxmd.com/read/28945977/trp-channels-as-potential-drug-targets
#13
Magdalene M Moran
The transient receptor potential (TRP) superfamily of channels comprises a diverse group of cation channels. Four TRP channel subunits coassemble to form functional homo- or heterotetramers that pass sodium, calcium, or both in the inward direction. Modulating TRP channel activity provides an important way to impact cellular function by regulating both membrane excitability and intracellular calcium levels. The import of these channels is underscored by the number of genetic diseases caused when they are mutated: Skeletal, skin, sensory, ocular, cardiac, and neuronal disturbances all arise from aberrant TRP function...
September 25, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28933692/a-quantitative-hypermorphic-cngc-allele-confers-ectopic-calcium-flux-and-impairs-cellular-development
#14
David M Chiasson, Kristina Haage, Katharina Sollweck, Andreas Brachmann, Petra Dietrich, Martin Parniske
The coordinated control of Ca(2+) signaling is essential for development in eukaryotes. Cyclic nucleotide-gated channel (CNGC) family members mediate Ca(2+) influx from cellular stores in plants(1-4). Here we report the unusual genetic behavior of a quantitative gain-of-function CNGC mutation (brush) in Lotus japonicus resulting in a leaky tetrameric channel. brush resides in a cluster of redundant CNGCs encoding subunits which resemble metazoan voltage-gated potassium (Kv1-Kv4) channels in assembly and gating properties...
September 21, 2017: ELife
https://www.readbyqxmd.com/read/28925404/ing5-activity-in-self-renewal-of-glioblastoma-stem-cells-via-calcium-and-follicle-stimulating-hormone-pathways
#15
F Wang, A Y Wang, C Chesnelong, Y Yang, A Nabbi, S Thalappilly, V Alekseev, K Riabowol
Stem cell-like brain tumor initiating cells (BTICs) cause recurrence of glioblastomas, with BTIC 'stemness' affected by epigenetic mechanisms. The ING family of epigenetic regulators (ING1-5) function by targeting histone acetyltransferase (HAT) or histone deacetylase complexes to the H3K4me3 mark to alter histone acetylation and subsequently, gene expression. Here we find that ectopic expression of ING5, the targeting subunit of HBO1, MOZ and MORF HAT complexes increases expression of the Oct4, Olig2 and Nestin stem cell markers, promotes self-renewal, prevents lineage differentiation and increases stem cell pools in BTIC populations...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28921675/altered-cav1-2-function-in-the-timothy-syndrome-mouse-model-produces-ascending-serotonergic-abnormalities
#16
Daniel G Ehlinger, Kathryn G Commons
Polymorphism in the gene CACNA1C, encoding the pore-forming subunit of Cav1.2 L-type calcium channels, has one of the strongest genetic linkages to schizophrenia, bipolar disorder and major depressive disorder: psychopathologies in which serotonin signaling has been implicated. Additionally, a gain-of-function mutation in CACNA1C is responsible for the neurodevelopmental disorder Timothy syndrome that presents with prominent behavioral features on the autism spectrum. Given an emerging role for serotonin in the etiology of autism spectrum disorders (ASD), we investigate the relationship between Cav1...
October 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28913875/alterations-in-the-%C3%AE-2-%C3%AE-ligand-thrombospondin-1-in-a-rat-model-of-spontaneous-absence-epilepsy-and-in-patients-with-idiopathic-genetic-generalized-epilepsies
#17
Ines Santolini, Roberta Celli, Milena Cannella, Tiziana Imbriglio, Michela Guiducci, Pasquale Parisi, Julian Schubert, Michele Iacomino, Federico Zara, Holger Lerche, Slavianka Moyanova, Richard Teke Ngomba, Gilles van Luijtelaar, Giuseppe Battaglia, Valeria Bruno, Pasquale Striano, Ferdinando Nicoletti
OBJECTIVES: Thrombospondins, which are known to interact with the α2 δ subunit of voltage-sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin-1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs)...
September 15, 2017: Epilepsia
https://www.readbyqxmd.com/read/28900128/the-l-type-voltage-gated-calcium-channel-co-localizes-with-syntaxin-1a-in-nano-clusters-at-the-plasma-membrane
#18
Julia Sajman, Michael Trus, Daphne Atlas, Eilon Sherman
The secretory signal elicited by membrane depolarization traverses from the Ca(2+)-bound α11.2 pore-forming subunit of the L-type Ca(2+)-channel (Cav1.2) to syntaxin 1 A (Sx1A) via an intra-membrane signaling mechanism. Here, we report the use of two-color Photo-Activated-Localization-Microscopy (PALM) to determine the relation between Cav1.2 and Sx1A in single-molecule detail. We observed nanoscale co-clusters of PAmCherry-tagged Sx1A and Dronpa-tagged α11.2 at a ~1:1 ratio. PAmCherry-tagged Sx1A(C145A), or PAmCherry-tagged Sx2, an inactive Cav1...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878628/early-correlated-network-activity-in-the-hippocampus-its-putative-role-in-shaping-neuronal-circuits
#19
REVIEW
Marilena Griguoli, Enrico Cherubini
Synchronized neuronal activity occurring at different developmental stages in various brain structures represents a hallmark of developmental circuits. This activity, which differs in its specific patterns among animal species may play a crucial role in de novo formation and in shaping neuronal networks. In the rodent hippocampus in vitro, the so-called giant depolarizing potentials (GDPs) constitute a primordial form of neuronal synchrony preceding more organized forms of activity such as oscillations in the theta and gamma frequency range...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28865873/statin-therapy-exacerbates-alcohol-induced-constriction-of-cerebral-arteries-via-modulation-of-ethanol-induced-bk-channel-inhibition-in-vascular-smooth-muscle
#20
Maria N Simakova, Shivantika Bisen, Alex M Dopico, Anna N Bukiya
Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo...
September 1, 2017: Biochemical Pharmacology
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