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N-type calcium channels

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https://www.readbyqxmd.com/read/28733833/neuroanatomy-of-pain-deficiency-and-cross-modal-activation-in-calcium-channel-subunit-cacn-%C3%AE-2%C3%AE-3-knockout-mice
#1
Julia Landmann, Franziska Richter, Ana-Maria Oros-Peusquens, N Jon Shah, Joseph Classen, G Gregory Neely, Angelika Richter, Josef M Penninger, Ingo Bechmann
The phenotype of calcium channel subunit (CACN) α2δ3 knockout (KO) mice includes sensory cross-activation and deficient pain perception. Sensory cross-activation defines the activation of a sensory cortical region by input from another modality due to reorganization in the brain such as after sensory loss. To obtain mechanistic insight into both phenomena, we employed a comprehensive battery of neuroanatomical techniques. While CACNα2δ3 was ubiquitously expressed in wild-type mice, it was absent in α2δ3 KO animals...
July 21, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28720324/synthesis-and-diabetic-neuropathic-pain-alleviating-effects-of-2n-pyrazol-3-yl-methylbenzo-d-isothiazole-1-1-dioxide-derivatives
#2
Jin Ri Hong, Young Jin Choi, Gyochang Keum, Ghilsoo Nam
A novel series of fused-benzensulfonamide 2-N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives was designed and synthesized as metabolically stable T-type calcium channel inhibitors. Several compounds, 9, 10, and 17, displayed potent T-type channel inhibitory activity. Among them, compounds 10 and 17 showed good metabolic stability in human liver microsomes, and low hERG channel and CYP450 inhibition. Compound 10 exhibited diabetic neuropathic pain-alleviating effects in a streptozotocin-induced peripheral diabetic neuropathy (PDN) model...
July 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28696432/cross-disorder-risk-gene-cacna1c-differentially-modulates-susceptibility-to-psychiatric-disorders-during-development-and-adulthood
#3
N Dedic, M L Pöhlmann, J S Richter, D Mehta, D Czamara, M W Metzger, J Dine, B T Bedenk, J Hartmann, K V Wagner, A Jurik, L M Almli, A Lori, S Moosmang, F Hofmann, C T Wotjak, G Rammes, M Eder, A Chen, K J Ressler, W Wurst, M V Schmidt, E B Binder, J M Deussing
Single-nucleotide polymorphisms (SNPs) in CACNA1C, the α1C subunit of the voltage-gated L-type calcium channel Cav1.2, rank among the most consistent and replicable genetics findings in psychiatry and have been associated with schizophrenia, bipolar disorder and major depression. However, genetic variants of complex diseases often only confer a marginal increase in disease risk, which is additionally influenced by the environment. Here we show that embryonic deletion of Cacna1c in forebrain glutamatergic neurons promotes the manifestation of endophenotypes related to psychiatric disorders including cognitive decline, impaired synaptic plasticity, reduced sociability, hyperactivity and increased anxiety...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28677901/big-conductance-calcium-activated-potassium-channel-openers-control-spasticity-without-sedation
#4
David Baker, Gareth Pryce, Cristina Visintin, Sofia Sisay, Alexander I Bondarenko, W S Vanessa Ho, Samuel J Jackson, Thomas E Williams, Sarah Al-Izki, Ioanna Sevastou, Masahiro Okuyama, Wolfgang F Graier, Lesley A Stevenson, Carolyn Tanner, Ruth Ross, Roger G Pertwee, Christopher M Henstridge, Andrew J Irving, Jesse Schulman, Keith Powell, Mark D Baker, Gavin Giovannoni, David L Selwood
BACKGROUND AND PURPOSE: Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R...
July 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28677751/effects-of-rmf-on-bkca-and-kv-channels-in-basilar-arterial-smooth%C3%A2-muscle-cells-of-shr
#5
Yan-Fei Qian, Yang Wang, Wei-Wei Tian, Sheng Wang, Lei Zhao, Li Li, Ke-Tao Ma, Jun-Qiang Si
The current study observed the effects and investigated the mechanism of remifentanil (RMF) on the isolated cerebral basilar arteries of spontaneously hypertensive rats (SHR) and Wistar‑Kyoto (WKY) rats. A pressure myograph system was used to observe and compare the effects of different concentrations of RMF (10‑10‑10‑5 mol/l) on the diameter changes of freshly isolated cerebral basilar arteries, which have been pre‑shrunk by phenylephrine (PE), an endothelium‑independent vasoconstrictor. Vascular smooth‑muscle cells of the cerebral basilar artery (BASMCs) were freshly obtained via enzymolysis...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28669545/retrograde-synaptic-inhibition-is-mediated-by-%C3%AE-neurexin-binding-to-the-%C3%AE-2%C3%AE-subunits-of-n-type-calcium-channels
#6
Xia-Jing Tong, Eduardo Javier López-Soto, Lei Li, Haowen Liu, Daniel Nedelcu, Diane Lipscombe, Zhitao Hu, Joshua M Kaplan
The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. In C. elegans, post-synaptic Neurexin (NRX-1) and pre-synaptic Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits acetylcholine (ACh) release at neuromuscular junctions. Here, we show that the retrograde signal decreases ACh release by inhibiting the function of pre-synaptic UNC-2/CaV2 calcium channels. Post-synaptic NRX-1 binds to an auxiliary subunit of pre-synaptic UNC-2/CaV2 channels (UNC-36/α2δ), decreasing UNC-36 abundance at pre-synaptic elements...
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28667054/analysis-of-decreases-in-systemic-arterial-pressure-and-heart-rate-in-response-to-the-hydrogen-sulfide-donor-sodium-sulfide
#7
Kevin W Swan, Bryant Minkyu Song, Allen L Chen, Travis J Chen, Ryan A Chan, Bradley T Guidry, Prasad V G Katakam, Edmund K Kerut, Thomas D Giles, Philip Kadowitz
The actions of hydrogen sulfide (H2S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H2S are unclear in the anesthetized rat. The objective of the current study is to investigate the effect of H2S on the electrocardiogram and examine the relationship between H2S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous (iv) administration of the H2S donor sodium sulfide (Na2S) in the anesthetized Sprague-Dawley (SD) rat decreased MAP and HR and produced changes in respiratory function...
June 30, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28662295/%C3%AE-9-containing-nicotinic-acetylcholine-receptors-and-the-modulation-of-pain
#8
REVIEW
Arik J Hone, Denis Servent, J Michael McIntosh
Neuropathic pain is a complex and debilitating syndrome for which there are few effective pharmacological treatments. Opioid-based medications are initially effective for acute pain but tolerance to their analgesic effects quickly develops and long-term use often leads to physical dependence and addiction. Furthermore, neuropathic pain is generally resistant to non-steroidal anti-inflammatory drugs. Other classes of medications including antidepressants, antiepileptics, and voltage-gated calcium channel (VGCC) inhibitors are only partially effective in most patients, may be associated with significant side effects, and have few disease modifying effects on the underlying pathology...
June 29, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28658794/a-comparative-study-on-clinical-and-biochemical-parameters-in-amlodipine-and-cilnidipine-treated-hypertensive-patients
#9
Kiran Shetty, Ranjan Shetty, Lakshminarayana Bairy, Pragna Rao, Amruth Kiran, Manjunath Shetty, Deepak, Vidya Nayak
INTRODUCTION: Hypertension is a major health issue worldwide. Calcium Channel Blockers (CCBs) are the most commonly used antihypertensive agents. CCBs act on voltage-dependent calcium channels and they were categorized into two subclasses, Dihydropyridine (DHP) and non-Dihydropyridine (non-DHP) derivative. Amlodipine is a third generation L-type of DHP and Cilnidipine is a novel L/N-type of DHP CCB, both drugs have excellent pharmacological profiles with the unique actions. AIM: To study the clinical and biochemical profile in Amlodipine and Cilnidipine treated mild to moderate hypertensive patients...
May 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28658605/sociability-impairments-in-genetic-absence-epilepsy-rats-from-strasbourg-reversal-by-the-t-type-calcium-channel-antagonist-z944
#10
Mark T Henbid, Wendie N Marks, Madeline J Collins, Stuart M Cain, Terrance P Snutch, John G Howland
Childhood absence epilepsy (CAE) is associated with interictal co-morbid symptoms including abnormalities in social behaviour. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a model of CAE that exhibits physiological and behavioural alterations characteristic of the human disorder. However, it is unknown if GAERS display the social deficits often observed in CAE. Sociability in rodents is thought to be mediated by neural circuits densely populated with T-type calcium channels and GAERS contain a missense mutation in the Cav3...
June 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28656587/allele-specific-polymerase-chain-reaction-for-the-detection-of-single-nucleotide-polymorphism-in-amlodipine-induced-gingival-enlargement
#11
N Kala, S P K K Babu, J Manjeu, A Aadivalavan, R Khan
WHAT IS KNOWN AND OBJECTIVE: Studies indicate that there is an increased serum concentration of amlodipine (a calcium channel blocker used to treat hypertension and angina) in patients having mutant multidrug resistance 1 (MDR1) gene. Hence, genetic factors may play a very significant role in amlodipine-induced complications including gingival enlargement. CASE DESCRIPTION: Three patients with amlodipine-induced gingival enlargement showed improvement following drug substitution of amlodipine with enalapril (an angiotensin-converting enzyme inhibitor) and non-invasive periodontal therapy...
June 27, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28638351/transcranial-direct-current-stimulation-considerations-for-research-in-adolescent-depression
#12
REVIEW
Jonathan C Lee, Charles P Lewis, Zafiris J Daskalakis, Paul E Croarkin
Adolescent depression is a prevalent disorder with substantial morbidity and mortality. Current treatment interventions do not target relevant pathophysiology and are frequently ineffective, thereby leading to a substantial burden for individuals, families, and society. During adolescence, the prefrontal cortex undergoes extensive structural and functional changes. Recent work suggests that frontolimbic development in depressed adolescents is delayed or aberrant. The judicious application of non-invasive brain stimulation techniques to the prefrontal cortex may present a promising opportunity for durable interventions in adolescent depression...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28610891/n-butyldeoxynojirimycin-delays-motor-deficits-cerebellar-microgliosis-and-purkinje-cell-loss-in-a-mouse-model-of-mucolipidosis-type-iv
#13
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...
September 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
#14
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
#15
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
#16
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...
August 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28580512/comparative-effect-of-calcium-channel-blockers-on-glomerular-function-in-hypertensive-patients-with-diabetes-mellitus
#17
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
#18
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
#19
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
#20
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
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