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N-type calcium channel

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https://www.readbyqxmd.com/read/28610891/n-butyl-deoxynojirimycin-delays-motor-deficits-cerebellar-microgliosis-and-purkinje-cell-loss-in-a-mouse-model-of-mucolipidosis-type-iv
#1
Lauren C Boudewyn, Jakub Sikora, Ladislav Kuchar, Jana Ledvinova, Yulia Grishchuk, Shirley L Wang, Kostantin Dobrenis, Steven U Walkley
Mucolipidosis type IV (MLIV) is a lysosomal storage disease exhibiting progressive intellectual disability, motor impairment, and premature death. There is currently no cure or corrective treatment. The disease results from mutations in the gene encoding mucolipin-1, a transient receptor potential channel believed to play a key role in lysosomal calcium egress. Loss of mucolipin-1 and subsequent defects lead to a host of cellular aberrations, including accumulation of glycosphingolipids (GSLs) in neurons and other cell types, microgliosis and, as reported here, cerebellar Purkinje cell loss...
June 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28608537/inhibition-of-human-n-and-t-type-calcium-channels-by-an-ortho-phenoxyanilide-derivative-moniro-1
#2
Jeffrey R McArthur, Leonid Motin, Ellen C Gleeson, Sandro Spiller, Richard J Lewis, Peter J Duggan, Kellie L Tuck, David J Adams
BACKGROUND AND PURPOSE: Voltage-gated calcium channels are involved in peripheral and central nervous system nociception. N-type (Cav 2.2) and T-type (Cav 3.1, Cav 3.2 and Cav 3.3) voltage-gated calcium channels are particularly important in studying and treating pain and epilepsy. EXPERIMENTAL APPROACH: In this study, whole-cell patch clamp electrophysiology was used to assess the potency and mechanism of action of a novel ortho-phenoxylanilide derivative, MONIRO-1, against a panel of voltage-gated calcium channels including Cav 1...
June 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28603497/sigma-1-receptor-plays-a-negative-modulation-on-n-type-calcium-channel
#3
Kang Zhang, Zhe Zhao, Liting Lan, Xiaoli Wei, Liyun Wang, Xiaoyan Liu, Haitao Yan, Jianquan Zheng
The sigma-1 receptor is a 223 amino acids molecular chaperone with a single transmembrane domain. It is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes. By chaperone-mediated interactions with ion channels, G-protein coupled receptors and cell-signaling molecules, the sigma-1 receptor performs broad physiological and pharmacological functions. Despite sigma-1 receptors have been confirmed to regulate various types of ion channels, the relationship between the sigma-1 receptor and N-type Ca(2+) channel is still unclear...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28584287/rescue-of-impaired-sociability-and-anxiety-like-behavior-in-adult-cacna1c-deficient-mice-by-pharmacologically-targeting-eif2%C3%AE
#4
Z D Kabir, A Che, D K Fischer, R C Rice, B K Rizzo, M Byrne, M J Glass, N V De Marco Garcia, A M Rajadhyaksha
CACNA1C, encoding the Cav1.2 subunit of L-type Ca(2+) channels, has emerged as one of the most prominent and highly replicable susceptibility genes for several neuropsychiatric disorders. Cav1.2 channels play a crucial role in calcium-mediated processes involved in brain development and neuronal function. Within the CACNA1C gene, disease-associated single-nucleotide polymorphisms have been associated with impaired social and cognitive processing and altered prefrontal cortical (PFC) structure and activity. These findings suggest that aberrant Cav1...
June 6, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28580512/comparative-effect-of-calcium-channel-blockers-on-glomerular-function-in-hypertensive-patients-with-diabetes-mellitus
#5
Yayoi Nishida, Yasuo Takahashi, Kotoe Tezuka, Satoshi Takeuchi, Tomohiro Nakayama, Satoshi Asai
BACKGROUND: We conducted a retrospective cohort study to evaluate and compare the longitudinal effect of monotherapy with L-, L/T-, L/N-, and L/N/T-type calcium channel blockers (CCBs) on estimated glomerular filtration rate (eGFR), and to investigate the association of treatment duration with eGFR in diabetic patients with hypertension. METHODS: Using a clinical database, we identified new users of five CCBs, i.e. amlodipine (L-type, n = 693), nifedipine (L-type, n = 189), azelnidipine (L/T-type, n = 91), benidipine (L/N/T-type, n = 183), and cilnidipine (L/N-type, n = 61)...
June 3, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28578411/red-cell-distribution-width-as-a-significant-indicator-of-medication-and-prognosis-in-type-2-diabetic-patients
#6
Xiao-Fen Xiong, Yuan Yang, Xianghui Chen, Xuejing Zhu, Chun Hu, Yachun Han, Li Zhao, Fuyou Liu, Lin Sun
Whether red cell distribution width (RDW) can be a potential indicator for diabetic nephropathy (DN) is unknown. A total of 809 type 2 diabetes mellitus (T2D) patients were divided into 4 groups according to the quartiles (Q) of the RDW (%): Q1 ≤ 12.4 (n = 229), 12.4 < Q2 ≤ 12.9 (n = 202), 12.9 < Q3 < 13.5 (n = 168), Q4 ≥ 13.5 (n = 210). Results showed that the levels in Q4 group was higher in age, disease duration, systolic blood pressure, blood urea nitrogen, creatinine, uric acid and proteinuria but lower in hemoglobin, serum albumin and glycosylated hemoglobin compared to Q1 group...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28553205/dopamine-and-serotonin-induced-modulation-of-gabaergic-and-glutamatergic-transmission-in-the-striatum-and-basal-forebrain
#7
REVIEW
Toshihiko Momiyama, Takuma Nishijo
Catecholamine receptor-mediated modulation of glutamatergic or GABAergic transmission in the striatum as well as basal forebrain (BF) has been intensively studied during these two decades. In the striatum, activation of dopamine (DA) D2 receptors in GABAergic terminals inhibits GABA release onto cholinergic interneurons by selective blockade of N-type calcium channels. In the BF, glutamatergic transmission onto cholinergic projection neurons is inhibited via DA D1-like receptors by selective blockade of P/Q-type calcium channels...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28530234/n-alkylated-analogs-of-4-methylamphetamine-4-ma-differentially-affect-monoamine-transporters-and-abuse-liability
#8
Ernesto Solis, John S Partilla, Farhana Sakloth, Iwona Ruchala, Kathryn L Schwienteck, Louis J De Felice, Jose M Eltit, Richard A Glennon, S Stevens Negus, Michael H Baumann
Clandestine chemists synthesize novel stimulant drugs by exploiting structural templates known to target monoamine transporters for dopamine, norepinephrine and serotonin (DAT, NET, and SERT, respectively). 4-Methylamphetamine (4-MA) is an emerging drug of abuse that interacts with transporters, but limited structure-activity data are available for its analogs. Here we employed uptake and release assays in rat brain synaptosomes, voltage-clamp current measurements in cells expressing transporters, and calcium flux assays in cells co-expressing transporters and calcium channels to study the effects of increasing N-alkyl chain length of 4-MA on interactions at DAT, NET and SERT...
May 22, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28515322/g%C3%AE-%C3%AE-directly-modulates-vesicle-fusion-by-competing-with-synaptotagmin-for-binding-to-neuronal-snare-proteins-embedded-in-membranes
#9
Zack Zurawski, Brian Page, Michael C Chicka, Rebecca L Brindley, Christopher A Wells, Anita M Preininger, Karren Hyde, James A Gilbert, Osvaldo Cruz-Rodriguez, Kevin P M Currie, Edwin R Chapman, Simon Alford, Heidi E Hamm
Gi/o-coupled GPCRs can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gβγ-mediated modulation of voltage-gated calcium channels(VGCC), inhibition can also be mediated through the direct interaction of Gβγ subunits with the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gβγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin(syt)1 for binding sites on t-SNARE...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28513286/azelnidipine-is-a-useful-medication-for-the-treatment-of-heart-failure-preserved-ejection-fraction
#10
Shunsuke Kiuchi, Shinji Hisatake, Takayuki Kabuki, Takashi Oka, Shintaro Dobashi, Takahiro Fujii, Takanori Ikeda
BACKGROUND: The optimal therapy in patients with heart failure preserved ejection fraction (HFpEF) and hypertension (HT) has not been revealed. The beta blocker (BB) and the renin angiotensin aldosterone system inhibitor (RAAS-I) are recommend as class IIa in patients with HFpEF. The calcium channel blocker (CCB), a major anti-hypertensive drugs in Japan, is also recommend as class IIa in patients with HFpEF. However, the difference between azelnidipine, an L type CCB, and cilnidipine, an N type CCB, is unclear...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28512860/intrinsic-cellular-and-molecular-properties-of-in-vivo-hippocampal-synaptic-plasticity-are-altered-in-the-absence-of-key-synaptic-matrix-molecules
#11
Stephan Jansen, Christine Gottschling, Andreas Faissner, Denise Manahan-Vaughan
Hippocampal synaptic plasticity comprises a key cellular mechanism for information storage. In the hippocampus, both long-term potentiation (LTP) and long-term depression (LTD) are triggered by synaptic Ca(2+) -elevations that are typically mediated by the opening of voltage-gated cation channels, such as N-methyl-D-aspartate receptors (NMDAR), in the postsynaptic density. The integrity of the post-synaptic density is ensured by the extracellular matrix (ECM). Here, we explored whether synaptic plasticity is affected in adult behaving mice that lack the ECM proteins brevican, neurocan, tenascin-C and tenascin-R (TG)...
May 17, 2017: Hippocampus
https://www.readbyqxmd.com/read/28472069/detection-of-trpv4-channel-current-like-activity-in-fawn-hooded-hypertensive-fhh-rat-cerebral-arterial-muscle-cells
#12
Debebe Gebremedhin, David X Zhang, Dorothee Weihrauch, Nnamdi N Uche, David R Harder
The transient receptor potential vallinoid type 4 (TRPV4) is a calcium entry channel known to modulate vascular function by mediating endothelium-dependent vasodilation. The present study investigated if isolated cerebral arterial myocytes of the Fawn Hooded hypertensive (FHH) rat, known to display exaggerated KCa channel current activity and impaired myogenic tone, express TRPV4 channels at the transcript and protein level and exhibit TRPV4-like single-channel cationic current activity. Reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunostaining analysis detected the expression of mRNA transcript and translated protein of TRPV4 channel in FHH rat cerebral arterial myocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28459217/verapamil-augments-carmustine-and-irradiation-induced-senescence-in-glioma-cells-by-reducing-intracellular-reactive-oxygen-species-and-calcium-ion-levels
#13
Seok Won Ham, Hee-Young Jeon, Hyunggee Kim
Resistance to conventional therapies and frequent recurrence are the major obstacles to the treatment of high-grade gliomas, including glioblastoma. Thus, the development of new therapeutic strategies to overcome these obstacles is necessary to improve the treatment outcomes. In this study, we found that verapamil, a pan-adenosine triphosphate-binding cassette transporter and L-type voltage-dependent calcium channel inhibitor, sensitized U87MG glioma cells to carmustine- and irradiation-induced senescence. Furthermore, our results indicated that verapamil treatment, in combination with carmustine and irradiation, rendered U87MG glioma cells and several patient-derived glioma stem cells more sensitive to therapy-induced senescence than individual or dual-combination treatments...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28456310/deltamethrin-affects-the-expression-of-voltage-gated-calcium-channel-%C3%AE-1-subunits-and-the-locomotion-egg-laying-foraging-behavior-of-caenorhabditis-elegans
#14
Rune Zeng, Xing Yu, Xing Tan, Shan Ye, Zhong Ding
Deltamethrin belongs to the class of synthetic pyrethroids, which are being widely used as insecticides in agricultural practices. Voltage-gated sodium channels (VGSCs) are the primary targets of these chemicals for toxicity to insects. Caenorhabditis elegans (C. elegans) does not have VGSCs but is susceptible to deltamethrin. Recent findings have suggested that pyrethroids can affect voltage-gated calcium channels (VGCCs). However, it remains elusive whether deltamethrin induces toxicity to C. elegans via modulating the activity of VGCCs...
May 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28450909/impact-of-gabapentin-on-neuronal-high-voltage-activated-ca-2-channel-properties-of-injured-side-axotomized-and-adjacent-uninjured-dorsal-root-ganglions-in-a-rat-model-of-spinal-nerve-ligation
#15
Minmin Zhu, Xiaodi Sun, Xiaodong Chen, Hang Xiao, Manlin Duan, Jianguo Xu
The density and properties of ion channels in the injured axon and dorsal root ganglion (DRG) neuronal soma membrane change following nerve injury, which may result in the development of neuropathic pain. Gabapentin (GBP) is a drug for the first-line treatment of neuropathic pain. One of its therapeutic targets is the voltage-activated calcium channel (VACC). In the present study, the whole-cell patch clamp technique was used to examine the changes of high voltage-activated Ca(2+) (HVA-Ca(2+)) channels in DRG neurons from sham and neuropathic rats in the absence and presence of GBP...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28442546/modeled-structural-basis-for-the-recognition-of-%C3%AE-2-3-sialyllactose-by-soluble-klotho
#16
Jon D Wright, Sung-Wan An, Jian Xie, Joonho Yoon, Nicole Nischan, Jennifer J Kohler, Noelynn Oliver, Carmay Lim, Chou-Long Huang
Soluble Klotho (sKlotho) is the shed ectodomain of antiaging membrane Klotho that contains 2 extracellular domains KL1 and KL2, each of which shares sequence homology to glycosyl hydrolases. sKlotho elicits pleiotropic cellular responses with a poorly understood mechanism of actions. Notably, in injury settings, sKlotho confers cardiac and renal protection by down-regulating calcium-permeable transient receptor potential canonical type isoform 6 (TRPC6) channels in cardiomyocytes and glomerular podocytes. Inhibition of PI3K-dependent exocytosis of TRPC6 is thought to be the underlying mechanism, and recent studies showed that sKlotho interacts with α2-3-sialyllactose-containing gangliosides enriched in lipid rafts to inhibit raft-dependent PI3K signaling...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28442324/the-interactive-role-of-cb1-receptors-and-l-type-calcium-channels-in-hippocampal-long-term-potentiation-in-rats
#17
Hamidreza Komaki, Fargol Saadat, Siamak Shahidi, Abdolrahman Sarihi, Parisa Hasanein, Alireza Komaki
Long-term potentiation (LTP) of synaptic responses is a widely researched model of synaptic plasticity that occurs during learning and memory. The cannabinoid system is an endogenous system that modulate this kind of synaptic plasticity. In addition, voltage dependent calcium channels is essential for induction of LTP at some synapses in the hippocampus. However, there is currently debate over the interaction between L-type calcium channels and cannabinoid system on the synaptic plasticity. In this study, we examined the effects of an acute administration of the cannabinoid antagonist AM251 following a chronic administration of the Ca(2+) channel blocker verapamil on LTP induction in the hippocampal dentate gyrus(DG) of rats...
April 23, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28433656/impaired-endothelium-derived-hyperpolarization-type-relaxation-in-superior-mesenteric-arteries-isolated-from-female-otsuka-long-evans-tokushima-fatty-rats
#18
Takayuki Matsumoto, Shota Kobayashi, Makoto Ando, Shun Watanabe, Maika Iguchi, Kumiko Taguchi, Tsuneo Kobayashi
Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism of endothelium-dependent vasorelaxation, and little attention has been paid to the EDH-type responses in female metabolic syndrome such as that observed with type-2 diabetes. We previously reported that EDH-type relaxation was impaired in superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type-2 diabetes, however, the response was unclear in female OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was altered in superior mesenteric arteries isolated from female OLETF rats compared to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50-59 weeks...
July 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28420732/modulation-of-tmem16a-channel-activity-by-the-von-willebrand-factor-type-a-vwa-domain-of-the-calcium-activated-chloride-channel-regulator-1-clca1
#19
Monica Sala-Rabanal, Zeynep Yurtsever, Kayla N Berry, Colin G Nichols, Tom J Brett
Calcium-activated chloride channels (CaCCs) are key players in transepithelial ion transport and fluid secretion, smooth muscle constriction, neuronal excitability, and cell proliferation. The CaCC regulator 1 (CLCA1) modulates the activity of the CaCC TMEM16A/Anoctamin 1 (ANO1) by directly engaging the channel at the cell surface, but the exact mechanism is unknown. Here we demonstrate that the von Willebrand factor type A (VWA) domain within the cleaved CLCA1 N-terminal fragment is necessary and sufficient for this interaction...
June 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28411270/short-term-facilitation-at-a-detonator-synapse-requires-the-distinct-contribution-of-multiple-types-of-voltage-gated-calcium-channels
#20
Simon Chamberland, Alesya Evstratova, Katalin Tóth
Neuronal calcium elevations are shaped by several key parameters, including the properties, density, and the spatial location of voltage-gated calcium channels (VGCCs). These features allow presynaptic terminals to translate complex firing frequencies and tune the amount of neurotransmitter released. Although synchronous neurotransmitter release relies on both P/Q- and N-type VGCCs at hippocampal mossy fiber-CA3 synapses, the specific contribution of VGCCs to calcium dynamics, neurotransmitter release, and short-term facilitation remains unknown...
May 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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