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N-type calcium channel

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https://www.readbyqxmd.com/read/29341826/mu-opioid-receptors-inhibit-the-exercise-pressor-reflex-by-closing-n-type-calcium-channels-but-not-by-opening-girk-channels-in-rats
#1
Juan A Estrada, Marc P Kaufman
Mu opioid G-protein coupled receptors (MOR) interact with ion channels to decrease neuronal excitability. In humans, intrathecal administration of the MOR agonist, fentanyl, inhibits the exercise pressor reflex, an effect that can be attributed to either the opening of inward rectifying potassium channels (GIRK) or the closing of N-type calcium channels. The purpose of this study was to determine if the highly selective MOR agonist DAMGO attenuates the exercise pressor reflex, and which of these two channels are responsible for this effect...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29335069/functional-roles-of-glutamic-acid-e143-and-e705-residues-in-the-n-terminus-and-transmembrane-domain-7-of-anoctamin-1-in-calcium-and-noxious-heat-sensing
#2
Jonghyun Choi, Yongwoo Jang, Haedong Kim, Jungwon Wee, Sinyoung Cho, Woo Sung Son, Sung Min Kim, Young Duk Yang
Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic Ca2+ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by Ca2+ and heat remain more elusive. To investigate critical amino acid residues for modulation of Ca2+ and heat sensing, we constructed a randomized mutant library for ANO1. Among 695 random mutants, reduced Ca2+ sensitivity was observed in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced sensitivity to Ca2+ but not to high temperatures, whereas the E705V mutant exhibited reduced sensitivity to both Ca2+ and noxious heat...
January 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29288665/intact-calcium-signaling-in-adrenergic-deficient-embryonic-mouse-hearts
#3
Jessica N Peoples, David G Taylor, Alexander N Katchman, Steven N Ebert
Mouse embryos that lack the ability to produce the adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to disruption of the dopamine beta-hydroxylase (Dbh-/-) gene inevitably perish from heart failure during mid-gestation. Since adrenergic stimulation is well-known to enhance calcium signaling in developing as well as adult myocardium, and impairments in calcium signaling are typically associated with heart failure, we hypothesized that adrenergic-deficient embryonic hearts would display deficiencies in cardiac calcium signaling relative to adrenergic-competent controls at a developmental stage immediately preceding the onset of heart failure, which first appears beginning or shortly after mouse embryonic day 10...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29237099/calcium-channel-blockers-for-primary-and-secondary-raynaud-s-phenomenon
#4
REVIEW
Fadumo Rirash, Paul C Tingey, Sarah E Harding, Lara J Maxwell, Elizabeth Tanjong Ghogomu, George A Wells, Peter Tugwell, Janet Pope
BACKGROUND: Raynaud's phenomenon is a vasospastic disease characterized by digital pallor, cyanosis, and extremity pain. Primary Raynaud's phenomenon is not associated with underlying disease, but secondary Raynaud's phenomenon is associated with connective tissue disorders such as systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease. Calcium channel blockers promote vasodilation and are commonly used when drug treatment for Raynaud's phenomenon is required...
December 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29225324/effects-of-cilnidipine-an-l-n-type-calcium-channel-blocker-on-carotid-atherosclerosis-in-japanese-post-stroke-hypertensive-patients-results-from-the-ca-attend-study
#5
Tomohisa Nezu, Naohisa Hosomi, Shiro Aoki, Noriyuki Suzuki, Tsukasa Teshima, Hitoshi Sugii, Shinobu Nagahama, Yoshiki Kurose, Hirofumi Maruyama, Masayasu Matsumoto
AIMS: Although several antihypertensive agents reduced the carotid intima-media thickness (IMT), it remains unclear whether those agents affect the interadventitial diameter (IAD). We aimed to examine whether cilnidipine, an L/N-type calcium channel blocker, reduced the common carotid IMT or IAD in post-stroke hypertensive patients. METHODS: The common carotid IMT and IAD were measured at the start of cilnidipine treatment and 12 months from that. The changes in the mean max-IMT or IAD between baseline and the 12-month follow-up were evaluated and compared between the thick group (max-IMT ≥1...
December 9, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29204711/voltage-sensitive-potassium-channels-of-the-bk-type-and-their-coding-genes-are-alcohol-targets-in-neurons
#6
Alex M Dopico, Anna N Bukiya, Jill C Bettinger
Among all members of the voltage-gated, TM6 ion channel superfamily, the proteins that constitute calcium- and voltage-gated potassium channels of large conductance (BK) and their coding genes are unique for their involvement in ethanol-induced disruption of normal physiology and behavior. Moreover, in vitro studies document that BK activity is modified by ethanol with an EC50~23 mM, which is near blood alcohol levels considered legal intoxication in most states of the USA (0.08 g/dL = 17.4 mM). Following a succinct introduction to our current understanding of BK structure and function in central neurons, with a focus on neural circuits that contribute to the neurobiology of alcohol use disorders (AUD), we review the modifications in organ physiology by alcohol exposure via BK and the different molecular elements that determine the ethanol response of BK in alcohol-naïve systems, including the role of an ethanol-recognizing site in the BK-forming slo1 protein, modulation of accessory BK subunits, and their coding genes...
December 5, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29198756/cav2-2-gates-calcium-independent-but-voltage-dependent-secretion-in-mammalian-sensory-neurons
#7
Zuying Chai, Changhe Wang, Rong Huang, Yuan Wang, Xiaoyu Zhang, Qihui Wu, Yeshi Wang, Xi Wu, Lianghong Zheng, Chen Zhang, Wei Guo, Wei Xiong, Jiuping Ding, Feipeng Zhu, Zhuan Zhou
Action potential induces membrane depolarization and triggers intracellular free Ca2+ concentration (Ca2+)-dependent secretion (CDS) via Ca2+ influx through voltage-gated Ca2+ channels. We report a new type of somatic exocytosis triggered by the action potential per se-Ca2+-independent but voltage-dependent secretion (CiVDS)-in dorsal root ganglion neurons. Here we uncovered the molecular mechanism of CiVDS, comprising a voltage sensor, fusion machinery, and their linker. Specifically, the voltage-gated N-type Ca2+ channel (CaV2...
November 23, 2017: Neuron
https://www.readbyqxmd.com/read/29186967/calcium-signaling-involved-in-bovine-herpesvirus-1-replication-in-mdbk-cells
#8
L Zhu, L Huang, Y Zhu, X Ding, G Zhu
Calcium is one of the most prominent second messengers in eukaryotic cells. The involvement of calcium signaling in bovine herpesvirus 1 (BoHV-1) replication was not yet reported. In this study, we revealed that the L-type Ca2+ calcium channel blocker, Verapamil and store-operated calcium channel blocker, 2-aminoethyl diphenylborinate (2-APB) inhibited BoHV-1 replication in MDBK cells at the post-entry stages, and the Na+/Ca²+ exchanger inhibitor, N-arachidonoyl glycine exchanger (NAGly) interfered with the viral entry process...
2017: Acta Virologica
https://www.readbyqxmd.com/read/29186694/large-scale-cognitive-gwas-meta-analysis-reveals-tissue-specific-neural-expression-and-potential-nootropic-drug-targets
#9
Max Lam, Joey W Trampush, Jin Yu, Emma Knowles, Gail Davies, David C Liewald, John M Starr, Srdjan Djurovic, Ingrid Melle, Kjetil Sundet, Andrea Christoforou, Ivar Reinvang, Pamela DeRosse, Astri J Lundervold, Vidar M Steen, Thomas Espeseth, Katri Räikkönen, Elisabeth Widen, Aarno Palotie, Johan G Eriksson, Ina Giegling, Bettina Konte, Panos Roussos, Stella Giakoumaki, Katherine E Burdick, Antony Payton, William Ollier, Ornit Chiba-Falek, Deborah K Attix, Anna C Need, Elizabeth T Cirulli, Aristotle N Voineskos, Nikos C Stefanis, Dimitrios Avramopoulos, Alex Hatzimanolis, Dan E Arking, Nikolaos Smyrnis, Robert M Bilder, Nelson A Freimer, Tyrone D Cannon, Edythe London, Russell A Poldrack, Fred W Sabb, Eliza Congdon, Emily Drabant Conley, Matthew A Scult, Dwight Dickinson, Richard E Straub, Gary Donohoe, Derek Morris, Aiden Corvin, Michael Gill, Ahmad R Hariri, Daniel R Weinberger, Neil Pendleton, Panos Bitsios, Dan Rujescu, Jari Lahti, Stephanie Le Hellard, Matthew C Keller, Ole A Andreassen, Ian J Deary, David C Glahn, Anil K Malhotra, Todd Lencz
Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29179637/cone-dystrophy-and-ectopic-synaptogenesis-in-a-cacna1f-loss-of-function-model-of-congenital-stationary-night-blindness-csnb2a
#10
D M Waldner, N C Giraldo Sierra, S Bonfield, L Nguyen, I S Dimopoulos, Y Sauvé, W K Stell, N T Bech-Hansen
Congenital stationary night blindness 2A (CSNB2A) is an X-linked retinal disorder, characterized by phenotypically variable signs and symptoms of impaired vision. CSNB2A is due to mutations in CACNA1F, which codes for the pore-forming α1F subunit of a L-type voltage-gated calcium channel, Cav1.4. Mouse models of CSNB2A, used for characterizing the effects of various Cacna1f mutations, have revealed greater severity of defects than in human CSNB2A. Specifically, Cacna1f-knockout mice show an apparent lack of visual function, gradual retinal degeneration, and disruption of photoreceptor synaptic terminals...
November 28, 2017: Channels
https://www.readbyqxmd.com/read/29169334/prevalence-and-treatment-of-diabetes-mellitus-and-hypertension-among-older-adults-with-intellectual-disability-in-comparison-with-the-general-population
#11
Anna Axmon, Gerd Ahlström, Peter Höglund
BACKGROUND: Diabetes mellitus and hypertension are risk factors for cardiovascular disease, which is the most common cause of death in the world. People with intellectual disability (ID) have been reported to have high rates of both these disorders. The aim of this study was to describe and compare prevalence ratios of diabetes mellitus and hypertension between older adults with ID and their age peers in the general population, and to describe and compare treatment patterns in these two groups...
November 23, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/29166837/-express-cisplatin-alters-the-function-and-expression-of-n-type-voltage-gated-calcium-channels-in-the-absence-of-morphological-damage-of-sensory-neurons
#12
Markus Leo, Linda-Isabell Schmitt, Holger Jastrow, Jürgen Thomale, Christoph Kleinschnitz, Tim Hagenacker
No abstract text is available yet for this article.
January 1, 2017: Molecular Pain
https://www.readbyqxmd.com/read/29166643/effects-of-l-and-n-type-ca-channel-blocker-cilnidipine-on-changes-in-heart-rate-and-qt-interval-during-dialysis
#13
Takeshi Iida, Satoshi Morimoto, Yoshifumi Amari, Takashi Ando, Atsuhiro Ichihara
BACKGROUND/AIMS: Hemodialysis patients have poor prognosis due to increased prevalence of cardiovascular diseases. Treatment to suppress increases in sympathetic nerve activity and QT prolongation may have the potential to reduce the occurrence of these events. The L/N-type Calcium (Ca) channel blocker cilnidipine has unique inhibitory action to inhibit sympathetic nerve activity and in a canine model ameliorates QT prolongation. In this study, we investigated whether cilnidipine has inhibitory effects on heart rate, an index of sympathetic nerve activity, and QT prolongation in patients undergoing dialysis...
November 22, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29163025/bdnf-trkb-induction-of-calcium-transients-through-cav2-2-calcium-channels-in-motoneurons-corresponds-to-f-actin-assembly-and-growth-cone-formation-on-%C3%AE-2-chain-laminin-221
#14
Benjamin Dombert, Stefanie Balk, Patrick Lüningschrör, Mehri Moradi, Rajeeve Sivadasan, Lena Saal-Bauernschubert, Sibylle Jablonka
Spontaneous Ca(2+) transients and actin dynamics in primary motoneurons correspond to cellular differentiation such as axon elongation and growth cone formation. Brain-derived neurotrophic factor (BDNF) and its receptor trkB support both motoneuron survival and synaptic differentiation. However, in motoneurons effects of BDNF/trkB signaling on spontaneous Ca(2+) influx and actin dynamics at axonal growth cones are not fully unraveled. In our study we addressed the question how neurotrophic factor signaling corresponds to cell autonomous excitability and growth cone formation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29138593/intrathecal-pain-management-a-team-based-approach
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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