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N-type calcium channel

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https://www.readbyqxmd.com/read/27913208/the-functions-of-store-operated-calcium-channels
#1
REVIEW
James W Putney, Natacha Steinckwich-Besançon, Takuro Numaga-Tomita, Felicity M Davis, Pooja N Desai, Diane M D'Agostin, Shilan Wu, Gary S Bird
Store-operated calcium channels provide calcium signals to the cytoplasm of a wide variety of cell types. The basic components of this signaling mechanism include a mechanism for discharging Ca(2+) stores (commonly but not exclusively phospholipase C and inositol 1,4,5-trisphosphate), a sensor in the endoplasmic reticulum that also serves as an activator of the plasma membrane channel (STIM1 and STIM2), and the store-operated channel (Orai1, 2 or 3). The advent of mice genetically altered to reduce store-operated calcium entry globally or in specific cell types has provided important tools to understand the functions of these widely encountered channels in specific and clinically important physiological systems...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27882454/portraying-the-effect-of-calcium-binding-proteins-on-cytosolic-calcium-concentration-distribution-fractionally-in-nerve-cells
#2
Brajesh Kumar Jha, Hardik Joshi, Devanshi D Dave
Nerve cells like neurons and astrocytes in central nervous system (CNS) take part in the signaling process which means the transformation of the information from one cell to another via signals. The signaling process is affected by various external parameters like buffers calcium-binding proteins, voltage-gated calcium channel. In the present paper, the role of buffers in the cytoplasmic calcium concentration distribution is shown. The elicitation in calcium concentration is due to the presence of lower amount calcium-binding proteins which can be shown graphically...
November 23, 2016: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/27861175/transient-receptor-potential-vanilloid-4-and-serum-glucocorticoid-regulated-kinase-1-are-critical-mediators-of-lung-injury-in-overventilated-mice-in-vivo
#3
Laura Michalick, Lasti Erfinanda, Ulrike Weichelt, Markus van der Giet, Wolfgang Liedtke, Wolfgang M Kuebler
BACKGROUND: Mechanical ventilation can cause lung endothelial barrier failure and inflammation cumulating in ventilator-induced lung injury. Yet, underlying mechanotransduction mechanisms remain unclear. Here, the authors tested the hypothesis that activation of the mechanosensitive Ca channel transient receptor potential vanilloid (TRPV4) by serum glucocorticoid-regulated kinase (SGK) 1 may drive the development of ventilator-induced lung injury. METHODS: Mice (total n = 54) were ventilated for 2 h with low (7 ml/kg) or high (20 ml/kg) tidal volumes and assessed for signs of ventilator-induced lung injury...
November 18, 2016: Anesthesiology
https://www.readbyqxmd.com/read/27831563/tissue-type-plasminogen-activator-controls-neuronal-death-by-raising-surface-dynamics-of-extrasynaptic-nmda-receptors
#4
Flavie Lesept, Arnaud Chevilley, Julie Jezequel, Laurent Ladépêche, Richard Macrez, Margaux Aimable, Sophie Lenoir, Thomas Bertrand, Laëtitia Rubrecht, Pascale Galea, Laurent Lebouvier, Karl-Uwe Petersen, Yannick Hommet, Eric Maubert, Carine Ali, Laurent Groc, Denis Vivien
N-methyl-d-aspartate receptors (NMDARs) are ion channels whose synaptic versus extrasynaptic localization critically influences their functions. This distribution of NMDARs is highly dependent on their lateral diffusion at the cell membrane. Each obligatory subunit of NMDARs (GluN1 and GluN2) contains two extracellular clamshell-like domains with an agonist-binding domain and a distal N-terminal domain (NTD). To date, the roles and dynamics of the NTD of the GluN1 subunit in NMDAR allosteric signaling remain poorly understood...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27823932/n-and-l-type-calcium-channels-blocker-cilnidipine-ameliorates-neuropathic-pain
#5
Shohei Yamamoto, Yuma Suzuki, Hideki Ono, Kazuhiko Kume, Masahiro Ohsawa
Cilnidipine is a dihydropyridine derivative that inhibits N-type and L-type voltage-gated Ca(2+) channels (VDCCs). We recently reported that a selective N-type VDCC blocker attenuated the spinal long-term potentiation (LTP) of C-fiber-evoked field potentials recorded in the spinal dorsal horn of rats, which served as a model for examining synaptic function during central pain sensitization. In this study, we investigated the effects of cilnidipine on the changes related to neuropathic pain induced by nerve injury...
November 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27823926/cisplatin-induced-neuropathic-pain-is-mediated-by-upregulation-of-n-type-voltage-gated-calcium-channels-in-dorsal-root-ganglion-neurons
#6
Markus Leo, Linda-Isabell Schmitt, Martin Erkel, Margarita Melnikova, Jürgen Thomale, Tim Hagenacker
Cisplatin is important in the treatment of various types of cancer. Although it is highly effective, it also has severe side effects, with neurotoxicity in dorsal root ganglion (DRG) neurons being one of the most common. The key mechanisms of neurotoxicity are still controversially discussed; however, disturbances of the calcium homeostasis in DRG neurons have been suggested to mediate cisplatin neurotoxicity. By using the whole-cell patch-clamp technique, immunostaining and behavioral experiments with Sprague-Dawley rats, we examined the influence of short- and long-term exposure to cisplatin on voltage-gated calcium channel (VGCC) currents (ICa(V)) in small DRG neurons...
November 5, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27821745/distinct-regions-that-control-ion-selectivity-and-calcium-dependent-activation-in-the-bestrophin-ion-channel
#7
George Vaisey, Alexandria N Miller, Stephen B Long
Cytoplasmic calcium (Ca(2+)) activates the bestrophin anion channel, allowing chloride ions to flow down their electrochemical gradient. Mutations in bestrophin 1 (BEST1) cause macular degenerative disorders. Previously, we determined an X-ray structure of chicken BEST1 that revealed the architecture of the channel. Here, we present electrophysiological studies of purified wild-type and mutant BEST1 channels and an X-ray structure of a Ca(2+)-independent mutant. From these experiments, we identify regions of BEST1 responsible for Ca(2+) activation and ion selectivity...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27799301/anoctamin-6-contributes-to-cl-secretion-in-accessory-cholera-enterotoxin-ace-stimulated-diarrhea-an-essential-role-for-pip2-signaling-in-cholera
#8
Joydeep Aoun, Mikio Hayashi, Irshad Ali Sheikh, Paramita Sarkar, Tultul Saha, Priyanka Ghosh, Rajsekhar Bhowmick, Dipanjan Ghosh, Tanaya Chatterjee, Pinak Chakrabarti, Manoj K Chakrabarti, Kazi Mirajul Hoque
Accessory cholera enterotoxin (Ace) of Vibrio cholerae has been shown to contribute to diarrhea However, the signaling mechanism and specific type of Cl- channel activated by Ace is yet unknown. We have shown here that the recombinant Ace protein induced ICl of apical plasma membrane which were inhibited by classical CaCC blockers. Surprisingly, Ace elicited rise of current was neither affected by Ano1 (Tmem16a) specific inhibitor T16A(inh)-AO1(TAO1) nor by CFTR blocker, CFTR inh-172. Ace stimulated whole-cell current in Caco-2 cells...
October 31, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27798760/rad-deletion-phenocopies-tonic-sympathetic-stimulation-of-the-heart
#9
Bryana M Levitan, Janet R Manning, Catherine N Withers, Jeffrey D Smith, Robin M Shaw, Douglas A Andres, Vincent L Sorrell, Jonathan Satin
Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad(-/-)) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad(-/-) confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad(-/-)...
October 31, 2016: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/27785644/effect-of-ica-l-blockade-on-adrenergic-stimulation-in-developing-heart
#10
T L Zefirov, A M Kuptsova, R G Biktemirova, N I Ziyatdinova, A L Zefirov
The effect of verapamil-induced blockade of L-type calcium ionic currents (ICa,L) on the action of non-selective adrenergic cardiac stimulation by norepinephrine was examined during different periods of early postnatal ontogeny. In 1-week-old rats, intravenous norepinephrine induced a short-term tachycardia both with and without preliminary injected verapamil. In 3-week-old rats, norepinephrine alone produced no chronotropic effect; in contrast, it induced a biphasic tachycardia in verapamil-treated rats. In 6- and 20-month-old rats, norepinephrine induced a short-term tachycardia, which could be prevented by verapamil...
October 26, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27782881/proteolytic-maturation-of-%C3%AE-2%C3%AE-represents-a-checkpoint-for-activation-and-neuronal-trafficking-of-latent-calcium-channels
#11
Ivan Kadurin, Laurent Ferron, Simon W Rothwell, James O Meyer, Leon R Douglas, Claudia S Bauer, Beatrice Lana, Wojciech Margas, Orpheas Alexopoulos, Manuela Nieto-Rostro, Wendy S Pratt, Annette C Dolphin
The auxiliary α2δ subunits of voltage-gated calcium channels are extracellular membrane-associated proteins, which are post-translationally cleaved into disulfide-linked polypeptides α2 and δ. We now show, using α2δ constructs containing artificial cleavage sites, that this processing is an essential step permitting voltage-dependent activation of plasma membrane N-type (CaV2.2) calcium channels. Indeed, uncleaved α2δ inhibits native calcium currents in mammalian neurons. By inducing acute cell-surface proteolytic cleavage of α2δ, voltage-dependent activation of channels is promoted, independent from the trafficking role of α2δ...
October 26, 2016: ELife
https://www.readbyqxmd.com/read/27780862/the-orai1-store-operated-calcium-channel-functions-as-a-hexamer
#12
Xiangyu Cai, Yandong Zhou, Robert M Nwokonko, Natalia A Loktionova, Xianming Wang, Ping Xin, Mohamed Trebak, Youjun Wang, Donald L Gill
Orai channels mediate store-operated Ca2+ signals crucial in regulating transcription in many cell types, and implicated in numerous immunological and inflammatory disorders. Despite their central importance, controversy surrounds the basic subunit structure of Orai channels, several biochemical and biophysical studies suggesting a tetrameric structure yet crystallographic evidence indicating a hexamer. We systematically investigated the subunit configuration of the functional Orai1 channel, generating a series of tdTomato-tagged concatenated Orai1 channel constructs (dimers to hexamers) expressed in CRISPR-derived Orai1-knockout HEK cells, stably expressing STIM1-YFP...
October 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27763693/progesterone-analogue-protects-stressed-photoreceptors-via-bfgf-mediated-calcium-influx
#13
Alice C Wyse-Jackson, Sarah L Roche, Ana M Ruiz-Lopez, Jennifer N Moloney, Ashleigh M Byrne, Thomas G Cotter
Retinitis pigmentosa (RP) is a degenerative retinal disease leading to photoreceptor cell loss. In 2011, our group identified the synthetic progesterone 'Norgestrel' as a potential treatment for RP. Subsequent research showed Norgestrel to work through progesterone receptor membrane component 1 (PGRMC1) activation and upregulation of neuroprotective basic fibroblast growth factor (bFGF). Using trophic factor deprivation of 661W photoreceptor-like cells, we aimed to further elucidate the mechanism leading to Norgestrel-induced neuroprotection...
October 20, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27754867/regulation-of-trpp3-channel-function-by-n-terminal-domain-palmitoylation-and-phosphorylation
#14
Wang Zheng, JungWoo Yang, Erwan Beauchamp, Ruiqi Cai, Shaimaa Hussein, Laura Hofmann, Qiang Li, Veit Flockerzi, Luc G Berthiaume, Jingfeng Tang, Xing-Zhen Chen
Transient receptor potential polycystin-3 (TRPP3) is a cation channel activated by calcium and proton and is involved in hedgehog signaling, intestinal development, and sour tasting. How TRPP3 channel function is regulated remains poorly understood. By N-terminal truncation mutations, electrophysiology, and Xenopus oocyte expression, we first identified fragment Asp-21-Ser-42 to be functionally important. We then found that deletion mutant Δ1-36 (TRPP3 missing fragment Met-1-Arg-36) has a similar function as wild-type TRPP3, whereas Δ1-38 is functionally dead, suggesting the importance of Val-37 or Cys-38...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27754221/os-32-06-mouse-glomerular-injury-reduced-by-blocking-n-type-calcium-channel
#15
Yu Guan, Daisuke Nakano, Zhang Yifan, Akira Nishiyama
OBJECTIVE: Previous studies have indicated the beneficial effects of N-type calcium channel blocker, cilnidipine, on protecting renal podocyte injury in metabolic syndrome model rats. In the present study, we examined the effects of cilnidipine (L/N-type calcium channel blocker) and nifedipine (L-type calcium channel blocker) on the glomerular filtration barrier damage in the doxorubicin-induced nephropathy mice model. DESIGN AND METHOD: Balb/c mice (male, 5 week-old) were treated with vehicle (n = 5), doxorubicin (20 mg/kg, i...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27754212/os-31-04-comparison-of-calcium-channel-blockers-versus-calcium-channel-blockers-with-renin-angiotensin-system-blockers-on-the-development-of-new-onset-diabetes-mellitus-in-hypertensive-patients
#16
Rha Seung-Woon, Choi Byoung Geol, Li Hu, Na Jin Oh, Choi Cheol Ung, Park Chang Gyu, Seo Hong Seog, Oh Dong Joo, Kim Yong Hoon, Her Ae-Young, Park Sang-Ho
OBJECTIVE: Recently several studies reported that anti-hypertensive drugs were associated with development of new-onset diabetes mellitus (NODM). However, data on the relationship between detailed prescription types and long-term incidence of NODM are still limited in Asian patients (pts). DESIGN AND METHOD: A total of 3,208 consecutive hypertension pts prescribed with calcium channel blockers (CCB) were enrolled with the exclusion of diabetic pts. Pts were divided into two groups according to the additional prescription of renin angiotensin system (RAS) blockers; 1) the CCB group (n = 1,987) and 2) CCB + RAS group (n = 1,221)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27754027/yia-03-03-effect-of-gabapentin-ligand-of-alpha-2-delta-subunit-of-voltage-dependent-calcium-channels-on-blood-pressure-and-baroreflex-sensitivity-in-spontaneously-hypertensive-rats-the-influence-of-guanethidine-induced-sympathectomy
#17
Michal Behuliak, Michal Bencze, Anna Vavrinova, Ivana Vaneckova, Josef Zicha
OBJECTIVE: Voltage-dependent calcium channels (VDCCs) play an important role in two major abnormalities observed in spontaneously hypertensive rats (SHR) - hyperactivity of sympathetic nervous system (SNS) and enhanced Ca influx to vascular smooth muscle cells (VSMC). α2δ subunit of VDCC, which promotes surface trafficking and modulates the biophysical properties of VDCC, was identified as a critical component of increased L-type VDCC calcium currents in arterial myocytes of SHR. On the other hand, N-type VDCCs control a neurotransmitter release in the peripheral sympathetic nervous system and play an important role in sympathetic hyperactivity in SHR...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27744004/histamine-h3-receptor-activation-stimulates-calcium-mobilization-in-a-subpopulation-of-rat-striatal-neurons-in-primary-culture-but-not-in-synaptosomes
#18
Nayeli Rivera-Ramírez, Wilber Montejo-López, María-Cristina López-Méndez, Agustín Guerrero-Hernández, Anayansi Molina-Hernández, Ubaldo García-Hernández, José-Antonio Arias-Montaño
The histamine H3 receptor (H3R) is abundantly expressed in the Central Nervous System where it regulates several functions pre and postsynaptically. H3Rs couple to Gαi/o proteins and trigger or modulate several intracellular signaling pathways, including the cAMP/PKA pathway and the opening of N- and P/Q-type voltage-gated Ca(2+) channels. In transfected cells, activation of the human H3R of 445 amino acids (hH3R445) results in phospholipase C (PLC) stimulation and release of Ca(2+) from intracellular stores...
December 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27734656/cilnidipine-next-generation-calcium-channel-blocker
#19
Mukesh Madhukar Shete
Hypertension is one of the most common conditions seen in primary care and a major public health problem in India. It can lead to various complications if not detected early and treated appropriately. As per the latest Eighth Joint National Committee (JNC 8) the goal BP in most hypertensive patients age <60 years should be <140/90 mmHg and treatment can be started by selecting drugs from among 4 specific medication classes i.e. angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), calcium channel blocker (CCB) or diuretics...
April 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27704354/differential-diagnostics-of-neoplastic-and-inflammatory-processes-in-the-brain-by-modifications-nmda-receptor-activity-in-blood-cells-with-verapamil-and-ketamine
#20
S P Syatkin, V A Frolov, N Ya Gridina, N G Draguntseva, A S Skorik
For the development of methods of additional differential diagnostics of gliomas of various grades of malignancy and gliomas and local inflammatory processes in the CNS we studied the intensity of aggregation of peripheral blood cells under the influence of channel blockers ketamine and verapamil. In in vitro experiments, verapamil and ketamine in various dilutions (from 10 to 100,000 times) were added to blood samples and the effects of these dilutions on the intensity of blood aggregation in patients with gliomas of different degree of malignancy, traumatic brain injuries, and other types of neurosurgical pathologies were studied...
September 2016: Bulletin of Experimental Biology and Medicine
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