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N-type calcium channel

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https://www.readbyqxmd.com/read/29767558/molecular-basis-of-the-counteraction-by-calcium-channel-blockers-of-cyclosporine-nephrotoxicity
#1
Safaa Hicham Hammoud, Sahar Alkhansa, Neamah Mahjoub, Amal Galal Omar, Mahmoud M El-Mas, Assaad A Eid
Nephrotoxicity is a serious side effect for the immunosuppressant drug cyclosporine (CSA). In this study, we tested the hypothesis that administration of calcium channel blockers such as verapamil or nifedipine ameliorate renal CSA-induced renal dysfunction. Furthermore, our study investigates the roles of inflammatory, oxidative, and fibrotic pathways in CSA-induced renal dysfunction. Six groups of male rats (n=6/group) were used and received one of the following treatments for 7 consecutive days: vehicle (cremophor EL, i...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29764972/separate-functional-properties-of-nmdars-regulate-distinct-aspects-of-spatial-cognition
#2
Erin M Sanders, Akua O Nyarko-Odoom, Kevin Zhao, Michael Nguyen, Hong Hong Liao, Matthew Keith, Jane Pyon, Alyssa Kozma, Mohima Sanyal, Daniel G McHail, Theodore C Dumas
N -methyl-d-aspartate receptors (NMDARs) at excitatory synapses are central to activity-dependent synaptic plasticity and learning and memory. NMDARs act as ionotropic and metabotropic receptors by elevating postsynaptic calcium concentrations and by direct intracellular protein signaling. In the forebrain, these properties are controlled largely by the auxiliary GluN2 subunits, GluN2A and GluN2B. While calcium conductance through NMDAR channels and intracellular protein signaling make separate contributions to synaptic plasticity, it is not known if these properties individually influence learning and memory...
June 2018: Learning & Memory
https://www.readbyqxmd.com/read/29746088/structure-activity-studies-reveal-the-molecular-basis-for-gabab-receptor-mediated-inhibition-of-high-voltage-activated-calcium-channels-by-%C3%AE-conotoxin-vc1-1
#3
Mahsa Sadeghi, Bodil B Carstens, Brid P Callaghan, James T Daniel, Han Shen Tae, Tracey O'Donnell, Joel Castro, Stuart M Brierley, David J Adams, David J Craik, Richard J Clark
α-Conotoxins are disulfide-bonded peptides from cone snail venoms and are characterized by their affinity for nicotinic acetylcholine receptors (nAChR). Several α-conotoxins with distinct selectivity for nAChR subtypes have been identified as potent analgesics in animal models of chronic pain. However, a number of α-conotoxins have been shown to inhibit N-type calcium channel currents in rodent dissociated dorsal root ganglion (DRG) neurons via activation of G protein-coupled GABAB receptors (GABABR). Therefore it is unclear whether activation of GABABR or inhibition of α9α10 nAChRs is the analgesic mechanism...
May 10, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29742403/alternative-splicing-at-n-terminus-and-domain-i-modulates-ca-v-1-2-inactivation-and-surface-expression
#4
Peter Bartels, Dejie Yu, Hua Huang, Zhenyu Hu, Stefan Herzig, Tuck Wah Soong
The CaV 1.2 L-type calcium channel is a key conduit for Ca2+ influx to initiate excitation-contraction coupling for contraction of the heart and vasoconstriction of the arteries and for altering membrane excitability in neurons. Its α1C pore-forming subunit is known to undergo extensive alternative splicing to produce many CaV 1.2 isoforms that differ in their electrophysiological and pharmacological properties. Here, we examined the structure-function relationship of human CaV 1.2 with respect to the inclusion or exclusion of mutually exclusive exons of the N-terminus exons 1/1a and IS6 segment exons 8/8a...
May 8, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29739832/expression-of-calcium-channel-transcripts-in-the-zebrafish-heart-dominance-of-t-type-channels
#5
Jaakko Haverinen, Minna Hassinen, Surjya Narayan Dash, Matti Vornanen
Calcium (Ca) channels are necessary for cardiac excitation-contraction (e-c) coupling, but Ca channel composition of fish hearts is still largely unknown. To this end, we determined transcript expression of Ca channels in the heart of zebrafish ( Danio rerio ), a popular model species. Altogether 18 Ca channel α-subunit genes were expressed in both atrium and ventricle. Transcripts for 7 L-type (Cav1.1a, Cav1.1b, Cav1.2, Cav1.3a, Cav1.3b, Cav1.4a, Cav1.4b), 5 T-type (Cav3.1, Cav3.2a, Cav3.2b, Cav3.3a, Cav3...
May 8, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29712850/distinct-gating-mechanism-of-soc-channel-involving-stim-orai-coupling-and-an-intramolecular-interaction-of-orai-in-caenorhabditis-elegans
#6
Kyu Min Kim, Tharaka Wijerathne, Jin-Hoe Hur, Uk Jung Kang, Ihn Hyeong Kim, Yeong Cheon Kweon, Ah Reum Lee, Su Ji Jeong, Sang Kwon Lee, Yoon Young Lee, Bo-Woong Sim, Jong-Hee Lee, Chunggi Baig, Sun-Uk Kim, Kyu-Tae Chang, Kyu Pil Lee, Chan Young Park
Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2+ signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Caenorhabditis elegans Orai channels...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29709527/upregulation-of-n-type-calcium-channels-in-the-soma-of-uninjured-dorsal-root-ganglion-neurons-contributes-to-neuropathic-pain-by-increasing-neuronal-excitability-following-peripheral-nerve-injury
#7
Jie Yang, Man-Xiu Xie, Li Hu, Xiao-Fang Wang, Jie-Zhen Mai, Yong-Yong Li, Ning Wu, Cheng Zhang, Jin Li, Rui-Ping Pang, Xian-Guo Liu
N-type voltage-gated calcium (Cav2.2) channels are expressed in the central terminals of dorsal root ganglion (DRG) neurons, and are critical for neurotransmitter release. Cav2.2 channels are also expressed in the soma of DRG neurons, where their function remains largely unknown. Here, we showed that Cav2.2 was upregulated in the soma of uninjured L4 DRG neurons, but downregulated in those of injured L5 DRG neurons following L5 spinal nerve ligation (L5-SNL). Local application of specific Cav2.2 blockers (ω-conotoxin GVIA, 1-100 μM or ZC88, 10-1000 μM) onto L4 and 6 DRGs on the operated side, but not the contralateral side, dose-dependently reversed mechanical allodynia induced by L5-SNL...
April 27, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29704319/a-molecule-based-genetic-association-approach-implicates-a-range-of-voltage-gated-calcium-channels-associated-with-schizophrenia
#8
Wen Li, Chun Chieh Fan, Tuomo Mäki-Marttunen, Wesley K Thompson, Andrew J Schork, Francesco Bettella, Srdjan Djurovic, Anders M Dale, Ole A Andreassen, Yunpeng Wang
Traditional genome-wide association studies (GWAS) have successfully detected genetic variants associated with schizophrenia. However, only a small fraction of heritability can be explained. Gene-set/pathway-based methods can overcome limitations arising from single nucleotide polymorphism (SNP)-based analysis, but most of them place constraints on size which may exclude highly specific and functional sets, like macromolecules. Voltage-gated calcium (Cav ) channels, belonging to macromolecules, are composed of several subunits whose encoding genes are located far away or even on different chromosomes...
April 28, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/29671419/trpm2-a-candidate-therapeutic-target-for-treating-neurological-diseases
#9
REVIEW
Jillian Corinne Belrose, Michael Frederick Jackson
Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca2+ )-permeable non-selective cation channel belonging to the TRP ion channel family. Oxidative stress-induced TRPM2 activation provokes aberrant intracellular Ca2+ accumulation and cell death in a variety of cell types, including neurons. Aberrant TRPM2 function has been implicated in several neurological disorders including ischemia/stroke, Alzheimer's disease, neuropathic pain, Parkinson's disease and bipolar disorder. In addition to research identifying a role for TRPM2 in disease, progress has been made in the identification of physiological functions of TRPM2 in the brain, including recent evidence that TRPM2 is necessary for the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression, an important form of synaptic plasticity at glutamate synapses...
April 19, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29667130/beneficial-effects-of-the-calcium-channel-blocker-ctk-01512-2-in-a-mouse-model-of-multiple-sclerosis
#10
Rodrigo B M Silva, Samuel Greggio, Gianina T Venturin, Jaderson C da Costa, Marcus V Gomez, Maria M Campos
Voltage-gated calcium channels (VGCCs) play a critical role in neuroinflammatory diseases, such as multiple sclerosis (MS). CTK 01512-2 is a recombinant version of the peptide Phα1β derived from the spider Phoneutria nigriventer, which inhibits N-type VGCC/TRPA1-mediated calcium influx. We investigated the effects of this molecule in the mouse model of experimental autoimmune encephalomyelitis (EAE). The effects of CTK 01512-2 were compared to those displayed by ziconotide-a selective N-type VGCC blocker clinically used for chronic pain-and fingolimod-a drug employed for MS treatment...
April 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29662677/auto-antibodies-against-p-q-and-n-type-voltage-dependent-calcium-channels-mimicking-frontotemporal-dementia
#11
Kyan Younes, Lauren A Lepow, Cynthia Estrada, Paul E Schulz
The behavioral variant of frontotemporal dementia is usually a sporadic and progressive neurodegenerative disorder. Here, we report the subacute onset of a frontotemporal dementia phenotype with a treatable etiology. The patient has a history of rheumatoid arthritis, episcleritis, and thyroid eye disease on immunosuppressive therapy. He experienced a rapid personality change, including inappropriate behavior, which suggested frontotemporal dementia. Results of imaging and neuropsychological testing also suggested frontotemporal dementia...
2018: SAGE Open Medical Case Reports
https://www.readbyqxmd.com/read/29655575/crmp2-neurofibromin-interface-drives-nf1-related-pain
#12
Aubin Moutal, Li Sun, Xiaofang Yang, Wennan Li, Song Cai, Shizhen Luo, Rajesh Khanna
An understudied symptom of the genetic disorder Neurofibromatosis type 1 (NF1) is chronic idiopathic pain. We used targeted editing of Nf1 in rats to provide direct evidence of a causal relationship between neurofibromin, the protein product of the Nf1 gene, and pain responses. Our study data identified a protein-interaction network with collapsin response meditator protein 2 (CRMP2) as a node and neurofibromin, syntaxin 1A, and the N-type voltage-gated calcium (CaV2.2) channel as interaction edges. Neurofibromin uncouples CRMP2 from syntaxin 1A...
April 12, 2018: Neuroscience
https://www.readbyqxmd.com/read/29623045/relaxin-deficiency-leads-to-uterine-artery-dysfunction-during-pregnancy-in-mice
#13
Sarah A Marshall, Sevvandi N Senadheera, Maria Jelinic, Kelly O'Sullivan, Laura J Parry, Marianne Tare
The uterine vasculature undergoes profound adaptations in response to pregnancy. Augmentation of endothelial vasodilator function and reduced smooth muscle reactivity are factors contributing to uterine artery adaptation and are critical for adequate placental perfusion. The peptide hormone relaxin has an important role in mediating the normal maternal renal vascular adaptations during pregnancy through a reduction in myogenic tone and an increase in flow-mediated vasodilation. Little is known however about the influence of endogenous relaxin on the uterine artery during pregnancy...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29622412/synthesis-and-evaluation-of-aminobenzothiazoles-as-blockers-of-n-and-t-type-calcium-channels
#14
Anjali Sairaman, Fernanda Caldas Cardoso, Anjie Bispat, Richard J Lewis, Peter J Duggan, Kellie L Tuck
Both N- and T-type calcium ion channels have been implicated in pain transmission and the N-type channel is a well-validated target for the treatment of neuropathic pain. An SAR investigation of a series of substituted aminobenzothiazoles identified a subset of five compounds with comparable activity to the positive control Z160 in a FLIPR-based intracellular calcium response assay measuring potency at both CaV 2.2 and CaV 3.2 channels. These compounds may form the basis for the development of drug leads and tool compounds for assessing in vivo effects of variable modulation of CaV 2...
March 19, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29614714/cloning-synthesis-and-functional-characterization-of-a-novel-%C3%AE-conotoxin-lt1-3
#15
Jinqin Chen, Li Liang, Huying Ning, Fengtao Cai, Zhuguo Liu, Longxiao Zhang, Liangyi Zhou, Qiuyun Dai
α-Conotoxins (α-CTxs) are small peptides composed of 11 to 20 amino acid residues with two disulfide bridges. Most of them potently and selectively target nicotinic acetylcholine receptor (nAChR) subtypes, and a few were found to inhibit the GABAB receptor (GABAB R)-coupled N-type calcium channels (Cav2.2). However, in all of α-CTxs targeting both receptors, the disulfide connectivity arrangement "C¹-C³, C²-C⁴" is present. In this work, a novel α4/7-CTx named Lt1.3 (GCCSHPACSGNNPYFC-NH₂) was cloned from the venom ducts of Conus litteratus ( C...
March 31, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29603093/oxaliplatin-modulates-the-characteristics-of-voltage-gated-calcium-channels-and-action-potentials-in-small-dorsal-root-ganglion-neurons-of-rats
#16
Linda-Isabell Schmitt, Markus Leo, Christoph Kleinschnitz, Tim Hagenacker
Oxaliplatin is important for treating colorectal cancer. Although oxaliplatin is highly effective, it has severe side effects, of which neurotoxicity in dorsal root ganglion (DRG) neurons is one of the most common. The key mechanisms of this neurotoxicity are still controversial. However, disturbances of calcium homeostasis in DRG neurons have been suggested to mediate oxaliplatin neurotoxicity. By using whole-cell patch-clamp and current-clamp techniques, as well as immunocytochemical staining, we examined the influence of short- and long-term exposure to oxaliplatin on voltage-gated calcium channels (VGCC) and different VGCC subtypes in small DRG neurons of rats in vitro...
March 30, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29593014/ryanodine-receptor-calcium-leak-in-circulating-b-lymphocytes-as-a-biomarker-in-heart-failure
#17
Alexander Kushnir, Gaetano Santulli, Steven R Reiken, Ellie Coromilas, Sarah J Godfrey, Danielle L Brunjes, Paolo C Colombo, Melana Yuzefpolskaya, Seth I Sokol, Richard N Kitsis, Andrew R Marks
Background -Advances in congestive heart failure (CHF) management depend on biomarkers for monitoring disease progression and therapeutic response. During systole, intracellular Ca2+ is released from the sarcoplasmic reticulum (SR) into the cytoplasm through type 2 ryanodine receptor/Ca2+ release channels (RyR2). In CHF, chronically elevated circulating catecholamine levels cause pathologic remodeling of RyR2 resulting in diastolic SR Ca2+ leak, and decreased myocardial contractility. Similarly, skeletal muscle contraction requires SR Ca2+ release through type-1 ryanodine receptors (RyR1), and chronically elevated catecholamine levels in CHF cause RyR1 mediated SR Ca2+ leak, contributing to myopathy and weakness...
March 28, 2018: Circulation
https://www.readbyqxmd.com/read/29584458/the-effect-of-an-l-n-type-calcium-channel-blocker-on-intradialytic-blood-pressure-in-intradialytic-hypertensive-patients
#18
Takayasu Ito, Naoki Fujimoto, Eiji Ishikawa, Kaoru Dohi, Mika Fujimoto, Tomohiro Murata, Michiyo Kiyohara, Hideyuki Takeuchi, Sukenari Koyabu, Hiroyuki Nishimura, Toshiaki Takeuchi, Masaaki Ito
BACKGROUND: Intradialytic hypertension (HTN), which is one of the poor prognostic markers in patients undergoing hemodialysis, may be associated with sympathetic overactivity. The L/N-type calcium channel blocker, cilnidipine, has been reported to suppress sympathetic nerves activity in vivo. Therefore, we hypothesized that cilnidipine could attenuate intradialytic systolic blood pressure (SBP) elevation. METHODS: Fifty-one patients on chronic hemodialysis who had intradialytic-HTN (SBP elevation ≥10 mmHg during hemodialysis) and no fluid overload were prospectively randomized into two groups: control and cilnidipine groups...
March 27, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29576117/a-neurosteroid-analogue-with-t-type-calcium-channel-blocking-properties-is-an-effective-hypnotic-but-is-not-harmful-to-neonatal-rat-brain
#19
N Atluri, S M Joksimovic, A Oklopcic, D Milanovic, J Klawitter, P Eggan, K Krishnan, D F Covey, S M Todorovic, V Jevtovic-Todorovic
BACKGROUND: More than 4 million children are exposed annually to sedatives and general anaesthetics (GAs) in the USA alone. Recent data suggest that common GAs can be detrimental to brain development causing neurodegeneration and long-term cognitive impairments. Challenged by a recent US Food and Drug Administration (FDA) warning about potentially neurotoxic effects of GAs in children, there is an urgent need to develop safer GAs. METHODS: Postnatal Day 7 (P7) rat pups of both sexes were exposed to six (repeated every 2 h) injections of equipotent hypnotic doses of ketamine or the neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) for 12 h...
April 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29562421/-downregulation-of-large-conductance-calcium-activated-potassium-channels-in-paraventricular-nucleus-contributes-to-sympathoexcitation-in-rats-with-chronic-heart-failure
#20
R J Wang, M L Wen, Q Zhou, X W Wei, H Li, Y B Zhao, Y F Qi, J Luan, X F Zhou
Objective: To elucidate the association between large conductance calcium-activated potassium channels (BKCa ) in the paraventricular hypothalamic nucleus (PVN) and sympathetic outflow in rats with chronic heart failure (CHF) . Methods: Male Wistar rats (6-7 weeks old) were randomized to sham operated group and CHF group (coronary artery ligation) . Two weeks after operation, BKCa inhibitor Iberiotoxin (IBTX) was infused into PVN by osmotic minipumps, rats were divided into following groups: sham+aCSF, CHF+aCSF, sham+low dose IBTX (0...
March 24, 2018: Zhonghua Xin Xue Guan Bing za Zhi
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