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N-type calcium channel

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https://www.readbyqxmd.com/read/29138593/intrathecal-pain-management-a-team-based-approach
#1
REVIEW
Jeremy A Adler, Neona M Lotz
Objective: Physician assistants (PAs), nurse practitioners (NPs), and registered nurses (RNs) provide professional services on pain management teams. This review provides an overview of the practical management of chronic pain with intrathecal (IT) therapy using an interprofessional approach (eg, physicians and other health care professionals), with a focus on the contributions of PAs, NPs, and RNs. Methods: Narrative review based on literature searches of the Medline database and treatment guidelines on the use of IT therapy in the management of patients with chronic pain...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29125390/responsiveness-of-voltage-gated-calcium-channels-in-sh-sy5y-human-neuroblastoma-cells-on-micropillar-substrates
#2
Wenxu Wang, Donghuo Zhong, Yu Lin, Rong Fan, Zhengjun Hou, Xiumei Cao, Yubin Ren
In this study, poly-L-lactic acid (PLLA) micropillar substrates were fabricated to evaluate the influence of topographic substrates on cell morphological and functional characteristics, such as spreading area, voltage-gated calcium channels (VGCCs) and membrane potential. The proliferation, spreading area, perimeter and circularity of SH-SY5Y cells interfaced with different substrates were first investigated. In addition, the cytoskeleton and focal adhesion of a cell as important manifestations of cell morphology were analyzed by immunofluorescence...
November 10, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/29123442/functional-effects-of-alagebrium-alt-711-isolated-rat-carotid-artery
#3
Cigdem Toprak, Basar Sirmagul, Semra Yigitaslan
Objective: In our study, the effects of glycosylated protein cross-link breaker, alagebrium was investigated on isolated rat carotid artery using myography. Alagebrium showed vasodilator effect on carotid artery rings; particularly, this effect was significantly increased in endothelium-intact rings. Materials and Methods: To clarify the vasodilator mechanism of alagebrium, different antagonists such as N(G)-Nitro-L-arginine methyl ester (L-NAME), glibenclamide, indomethacin, metoprolol, propranolol, tetraethylammonium, and calcium channel activator BAYK-8644 were used to reverse this effect...
October 2017: Eurasian Journal of Medicine
https://www.readbyqxmd.com/read/29123182/identification-of-a-novel-camp-dependent-protein-kinase-a-phosphorylation-site-on-the-human-cardiac-calcium-channel
#4
Henrietta Cserne Szappanos, Padmapriya Muralidharan, Evan Ingley, Jakob Petereit, Harvey A Millar, Livia C Hool
The "Fight or Flight" response is elicited by extrinsic stress and is necessary in many species for survival. The response involves activation of the β-adrenergic signalling pathway. Surprisingly the mechanisms have remained unresolved. Calcium influx through the cardiac L-type Ca(2+) channel (Cav1.2) is absolutely required. Here we identify the functionally relevant site for PKA phosphorylation on the human cardiac L-type Ca(2+) channel pore forming α1 subunit using a novel approach. We used a cell free system where we could assess direct effects of PKA on human purified channel protein function reconstituted in proteoliposomes...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116786/discovery-of-a-potent-selective-t-type-calcium-channel-blocker-as-a-drug-candidate-for-the-treatment-of-generalized-epilepsies
#5
Olivier Bezençon, Bibia Heidmann, Romain Siegrist, Simon Stamm, Sylvia Richard, Davide Pozzi, Olivier Corminboeuf, Catherine Roch, Melanie Kessler, Eric A Ertel, Isabelle Reymond, Thomas Pfeifer, Ruben de Kanter, Michael Toeroek-Schafroth, Luca G Moccia, Jacques Mawet, Richard Moon, Markus Rey, Bruno Capeleto, Elvire Fournier
We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as clinical candidate.
November 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29114718/ascertainment-of-self-reported-prescription-medication-use-compared-with-pharmaceutical-claims-data
#6
Danijela Gnjidic, Wei Du, Sallie-Anne Pearson, Sarah N Hilmer, Emily Banks
BACKGROUND: Evidence on the comparative validity of self-reported medication use in large-scale studies is limited. This study compared self-reported medication use of prescription-only medications to gold standard pharmaceutical claims (i.e. dispensing) data. METHODS: We selected a random sample of 500 participants from the 45 and Up Study, a large-scale Australian study, with complete ascertainment of Pharmaceutical Benefits Scheme dispensing records. Self-reported medication use was ascertained by questionnaire requesting data on medications used "for most of the last 4 weeks"...
October 11, 2017: Public Health Research & Practice
https://www.readbyqxmd.com/read/29094416/map6-interacts-with-tctex1-and-cav-2-2-n-type-calcium-channels-to-regulate-calcium-signaling-in-neurons
#7
Jacques Brocard, Fabrice Dufour, Sylvie Gory-Fauré, Christophe Arnoult, Christophe Bosc, Eric Denarier, Leticia Peris, Yasmina Saoudi, Michel De Waard, Annie Andrieux
MAP6 proteins were first described as microtubule-stabilizing agents, whose properties were thought to be essential for neuronal development and maintenance of complex neuronal networks. However, deletion of all MAP6 isoforms in MAP6 KO mice does not lead to dramatic morphological aberrations of the brain but rather to alterations in multiple neurotransmissions and severe behavioral impairments. A search for protein partners of MAP6 proteins identified Tctex1 - a dynein light chain with multiple non-microtubule-related functions...
November 2, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29055091/functional-interaction-of-junctophilin-2-with-small-conductance-ca-2-activated-potassium-channel-subtype-2-sk2-in-mouse-cardiac-myocytes
#8
Hong K Fan, Tian X Luo, Wei D Zhao, Yong H Mu, Yang Yang, Wen J Guo, Hui Y Tu, Qian Zhang
AIM: Junctophilins (JPs), a protein family of the junctional membrane complex, maintain the close conjunction between cell surface and intracellular membranes in striate muscle cells mediating the cross talk between extracellular Ca(2+) entry and intracellular Ca(2+) release. The small conductance Ca(2+) -activated K(+) channels are activated by the intracellular calcium and play an essential role in the cardiac action potential profile. Molecular mechanisms of regulation of the SK channels are still uncertain...
October 21, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29053695/targeting-cysteine-thiols-for-in-vitro-site-specific-glycosylation-of-recombinant-proteins
#9
Yoo Jung Choi, Jinhui Zhu, Steve Chung, Naveed Siddiqui, Qingping Feng, Peter B Stathopulos
Stromal interaction molecule-1 (STIM1) is a type-I transmembrane protein located on the endoplasmic reticulum (ER) and plasma membranes (PM). ER-resident STIM1 regulates the activity of PM Orai1 channels in a process known as store operated calcium (Ca(2+)) entry which is the principal Ca(2+) signaling process that drives the immune response. STIM1 undergoes post-translational N-glycosylation at two luminal Asn sites within the Ca(2+) sensing domain of the molecule. However, the biochemical, biophysical, and structure biological effects of N-glycosylated STIM1 were poorly understood until recently due to an inability to readily obtain high levels of homogeneous N-glycosylated protein...
October 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29045762/synthesis-and-determination-of-lipophilicity-anticonvulsant-activity-and-preliminary-safety-of-3-substituted-and-3-unsubstituted-n-4-arylpiperazin-1-yl-alkyl-pyrrolidine-2-5-dione-derivatives
#10
Sabina Rybka, Jolanta Obniska, Paweł Żmudzki, Paulina Koczurkiewicz, Katarzyna Wójcik-Pszczoła, Elżbieta Pękala, Adrian Bryła, Anna Rapacz
A new series of 1,3-substituted pyrrolidine-2,5-dione derivatives as potential anticonvulsant agents are described. Initial pharmacological screening of these compounds was performed by using acute models of seizures (MES and scPTZ tests) in mice after intraperitoneal administration. Quantitative pharmacological research revealed that the most promising compounds were N-[{4-(3-trifluoromethylphenyl)piperazin-1-yl}propyl]-3-benzhydrylpyrrolidine-2,5-dione monohydrochloride (11) with a ED50 value of 75.9 mg kg(-1) (MES test) and N-[{4-(3,4-dichlorophenyl)piperazin-1-yl}ethyl]-3-methylpyrrolidine-2,5-dione monohydrochloride (18) with ED50 =88...
October 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29038363/moderate-exercise-training-does-not-prevent-the-reduction-in-myocardial-l-type-ca-2-channels-protein-expression-at-obese-rats
#11
Vitor L da Silva, Ana P Lima-Leopoldo, Artur J T Ferron, Jóctan P Cordeiro, Paula P Freire, Dijon H S de Campos, Carlos R Padovani, Mário M Sugizaki, Antonio C Cicogna, André S Leopoldo
Authors have showed that obesity implicates cardiac dysfunction associated with myocardial L-type calcium channels (LTCCs) activity impairments, as well as moderate exercise training (MET) seems to be an important therapeutic tool. We tested the hypothesis that MET promotes improvements on LTCCS activity and protein expression at obesity induced by unsaturated high-fat diets, which could represent a protective effects against development of cardiovascular damage. Male Wistar rats were randomized in control (C, n = 40), which received a standard diet and obese (Ob; n = 40), which received high-fat diet...
October 2017: Physiological Reports
https://www.readbyqxmd.com/read/29038048/the-influence-of-doca-salt-hypertension-and-chronic-administration-of-the-faah-inhibitor-urb597-on-kca2-3-kca3-1-edh-type-relaxation-in-rat-small-mesenteric-arteries
#12
Monika Kloza, Marta Baranowska-Kuczko, Barbara Malinowska, Olga Karpińska, Ewa Harasim-Symbor, Irena Kasacka, Hanna Kozłowska
The aim of this study was to examine the influence of deoxycorticosterone acetate-salt (DOCA-salt) hypertension and chronic treatment with the fatty acid amide hydrolase inhibitor, URB597, on small and intermediate conductance calcium-activated potassium channels and endothelium-dependent hyperpolarization (KCa2.3/KCa3.1-EDH) in rat small mesenteric arteries (sMAs). The EDH-type response was investigated, in endothelium-intact sMAs using a wire myograph, by examining acetylcholine-evoked vasorelaxation in the presence of N(ω)-nitro-L-arginine methyl ester and indomethacin (inhibitors of nitric oxide synthase and cyclooxygenase, respectively)...
October 14, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/29033792/spontaneous-and-evoked-activity-from-murine-ventral-horn-cultures-on-microelectrode-arrays
#13
Bryan J Black, Rahul Atmaramani, Joseph J Pancrazio
Motor neurons are the site of action for several neurological disorders and paralytic toxins, with cell bodies located in the ventral horn (VH) of the spinal cord along with interneurons and support cells. Microelectrode arrays (MEAs) have emerged as a high content assay platform for mechanistic studies and drug discovery. Here, we explored the spontaneous and evoked electrical activity of VH cultures derived from embryonic mouse spinal cord on multi-well plates of MEAs. Primary VH cultures from embryonic day 15-16 mice were characterized by expression of choline acetyltransferase (ChAT) by immunocytochemistry...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29029787/early-testosterone-replacement-attenuates-intracellular-calcium-dyshomeostasis-in-the-heart-of-testosterone-deprived-male-rats
#14
Punate Weerateerangkul, Krekwit Shinlapawittayatorn, Siripong Palee, Nattayaporn Apaijai, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: Testosterone deficiency in elderly men increases the risk of cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired cardiac Ca(2+) regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important role of testosterone in cardiac Ca(2+) regulation. However, the temporal changes of Ca(2+) dyshomeostasis in testosterone-deprived conditions are unclear. Moreover, the effects of early vs. late testosterone replacement are unknown...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29019979/cryo-electron-microscopy-structure-of-the-lysosomal-calcium-permeable-channel-trpml3
#15
Marscha Hirschi, Mark A Herzik, Jinhong Wie, Yang Suo, William F Borschel, Dejian Ren, Gabriel C Lander, Seok-Yong Lee
The modulation of ion channel activity by lipids is increasingly recognized as a fundamental component of cellular signalling. The transient receptor potential mucolipin (TRPML) channel family belongs to the TRP superfamily and is composed of three members: TRPML1-TRPML3. TRPMLs are the major Ca(2+)-permeable channels on late endosomes and lysosomes (LEL). They regulate the release of Ca(2+) from organelles, which is important for various physiological processes, including organelle trafficking and fusion. Loss-of-function mutations in the MCOLN1 gene, which encodes TRPML1, cause the neurodegenerative lysosomal storage disorder mucolipidosis type IV, and a gain-of-function mutation (Ala419Pro) in TRPML3 gives rise to the varitint-waddler (Va) mouse phenotype...
October 19, 2017: Nature
https://www.readbyqxmd.com/read/28990373/sigma-1-receptor-agonist-increases-axon-outgrowth-of-hippocampal-neurons-via-voltage-gated-calcium-ions-channels
#16
Dong Li, Shu-Zhuo Zhang, Yu-Hong Yao, Yun Xiang, Xiao-Yun Ma, Xiao-Li Wei, Hai-Tao Yan, Xiao-Yan Liu
INTRODUCTION: Sigma-1 receptors (Sig-1Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig-1R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig-1R-mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig-1R on axon outgrowth are not fully understood. METHODS: To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured naïve hippocampal neurons before and after the application of the Sig-1R agonist, SA4503...
October 8, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28957379/involvement-of-parkin-in-the-ubiquitin-proteasome-system-mediated-degradation-of-n-type-voltage-gated-ca2-channels
#17
Lizbeth Grimaldo, Alejandro Sandoval, Edgar Garza-López, Ricardo Felix
N-type calcium (CaV2.2) channels are widely expressed in the brain and the peripheral nervous system, where they play important roles in the regulation of transmitter release. Although CaV2.2 channel expression levels are precisely regulated, presently little is known regarding the molecules that mediate its synthesis and degradation. Previously, by using a combination of biochemical and functional analyses, we showed that the complex formed by the light chain 1 of the microtubule-associated protein 1B (LC1-MAP1B) and the ubiquitin-proteasome system (UPS) E2 enzyme UBE2L3, may interact with the CaV2...
2017: PloS One
https://www.readbyqxmd.com/read/28949006/calcium-influx-through-trpv4-channels-modulates-the-adherens-contacts-between-retinal-microvascular-endothelial-cells
#18
Tam T T Phuong, Sarah N Redmon, Oleg Yarishkin, Jacob M Winter, Dean Y Li, David Križaj
KEY POINTS: Endothelial cells employ transient receptor potential isoform 4 (TRPV4) channels to sense ambient mechanical and chemical stimuli. In retinal microvascular endothelial cells, TRPV4 channels regulate calcium homeostasis, cytoskeletal signalling and the organization of adherens junctional contacts. Intracellular calcium increases induced by TRPV4 agonists include a significant contribution from calcium release from internal stores. Activation of TRPV4 channels regulates retinal endothelial barriers in vitro and in vivo...
November 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28904913/inhibition-by-benidipine-of-contractility-of-isolated-proximal-and-distal-caprine-ureter
#19
Sumith K Mathew, Girish S Naik, Jacob Peedicayil
CONTEXT: Benidipine is a calcium channel blocker that blocks all the major types (L, N, and T) of calcium channels. It has been shown to inhibit the contractility of many isolated smooth muscles but not isolated ureter. AIMS: This study evaluated the ability of benidipine to inhibit the spontaneous contractility of isolated proximal and distal caprine (goat) ureter. SETTINGS AND DESIGN: Spontaneous contractility of isolated goat ureter was recorded using a physiograph...
July 2017: International Journal of Applied and Basic Medical Research
https://www.readbyqxmd.com/read/28901828/protein-kinase-c-enhances-plasma-membrane-expression-of-cardiac-l-type-calcium-channel-cav1-2
#20
Tal Keren Raifman, Prabodh Kumar, Hannelore Haase, Enno Klussmann, Nathan Dascal, Sharon Weiss
L-type-voltage-dependent Ca(2+) channels (L-VDCCs; CaV1.2, α1C), crucial in cardiovascular physiology and pathology, are modulated via activation of G-protein-coupled receptors and subsequently protein kinase C (PKC). Despite extensive study, key aspects of the mechanisms leading to PKC-induced Ca(2+) current increase are unresolved. A notable residue, Ser1928, located in the distal C-terminus (dCT) of α1C was shown to be phosphorylated by PKC. CaV1.2 undergoes posttranslational modifications yielding full-length and proteolytically cleaved CT-truncated forms...
September 13, 2017: Channels
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