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N-type calcium channels

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https://www.readbyqxmd.com/read/28904913/inhibition-by-benidipine-of-contractility-of-isolated-proximal-and-distal-caprine-ureter
#1
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
#2
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
https://www.readbyqxmd.com/read/28899915/conditional-deletion-of-the-l-type-calcium-channel-cav1-2-in-ng2-positive-cells-impairs-remyelination-in-mice
#3
Diara A Santiago González, Veronica T Cheli, Norma N Zamora, Tenzing N Lama, Vilma Spreuer, Geoffrey G Murphy, Pablo M Paez
Exploring the molecular mechanisms that drive the maturation of oligodendrocyte progenitor cells (OPCs) during the remyelination process is essential to develop new therapeutic tools to intervene in demyelinating diseases such as Multiple Sclerosis. To determine whether L-type voltage-gated calcium channels (L-VGCCs) are required for OPC development during remyelination, we have generated an inducible conditional knockout mouse in which the L-VGCC isoform Cav1.2 was deleted in NG2 positive OPCs (Cav1.2(KO))...
September 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28894435/neuroactive-steroids-receptor-interactions-and-responses
#4
REVIEW
Kald Beshir Tuem, Tesfay Mehari Atey
Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs). NASs modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-d-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28882644/postsynaptic-n-type-or-p-q-type-calcium-channels-mediate-long-term-potentiation-by-group-i-metabotropic-glutamate-receptors-in-the-trigeminal-oralis
#5
Haein Weon, Tae Wan Kim, Dong-Ho Youn
AIMS: Both N-type and P/Q-type voltage-gated Ca(2+) channels (VGCCs) are involved in the induction of long-term potentiation (LTP), the long-lasting increase of synaptic strength, in the central nervous system. To provide further information on the roles of N-type and P/Q-type VGCCs in the induction of LTP at excitatory synapses of trigeminal primary afferents in the spinal trigeminal subnucleus oralis (Vo), we investigated whether they contribute to the induction of LTP by activation of group I metabotropic glutamate receptors (mGluRs)...
September 4, 2017: Life Sciences
https://www.readbyqxmd.com/read/28878678/verapamil-blocks-scopolamine-enhancement-effect-on-memory-consolidation-in-passive-avoidance-task-in-rats
#6
Verónica Giménez De Béjar, María Caballero Bleda, Natalija Popović, Miroljub Popović
Our recent data have indicated that scopolamine, a non-selective muscarinic receptor antagonist, improves memory consolidation, in a passive avoidance task, tested in rats. It has been found that verapamil, a phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, inhibits [3H] N-methyl scopolamine binding to M1 muscarinic receptors. However, there are no data about the effect of verapamil on memory consolidation in the passive avoidance task, in rats. The purpose of the present study was to examine the effects of verapamil (0...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28875959/downregulation-of-na-ca-2-exchanger-isoform-1-protects-isolated-hearts-by-sevoflurane-postconditioning-but-not-by-delayed-remote-ischemic-preconditioning-in-rats
#7
Yang Yu, Cheng-Hui Zhou, Yun-Tai Yao, Li-Huan Li
Background: Calcium regulatory proteins-L-type Ca(2+) channels (LTCCs), ryanodine receptor 2 (RyR2), and Na(+)/Ca(2+) exchanger isoform 1 (NCX1) have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury (I/RI). Both sevoflurane postconditioning (SevoPoC) and delayed remote ischemic preconditioning (DRIPC) have been shown to protect the heart against I/RI. In this study, we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model...
September 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28866764/l-type-calcium-channels-in-exocytosis-and-endocytosis-of-chromaffin-cells
#8
REVIEW
Carmen Nanclares, Andrés M Baraibar, Luis Gandía
The coexistence of different subtypes of voltage-dependent calcium channels (VDCC) within the same chromaffin cell (CC) and the marked interspecies variability in the proportion of VDCC subtypes that are present in the plasmalemma of the CCs raises the question on their roles in controlling different physiological functions. Particularly relevant seems to be the role of VDCCs in the regulation of the exocytotic neurotransmitter release process, and its tightly coupled membrane retrieval (endocytosis) process since both are Ca(2+)-dependent processes...
September 2, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28840637/reduction-in-microalbuminuria-by-calcium-channel-blockers-in-patients-with-type-2-diabetes-mellitus-and-hypertension-a-randomized-open-label-active-controlled-superiority-parallel-group-clinical-trial
#9
You-Cheol Hwang, Kun-Ho Yoon, Bong-Soo Cha, Kwan-Woo Lee, Hak Chul Jang, Kyung Wan Min, Choon Hee Chung, Moon-Kyu Lee
BACKGROUND: It has been suggested that renoprotection with calcium channel blockers (CCBs) may differ. This study aimed to compare the anti-proteinuric effect of different CCBs in patients with type 2 diabetes (T2D). METHODS: A multicentre, randomized, open-label, active-controlled study was performed in seven centres in Korea. A total of 74 patients with T2D and microalbuminuria treated with renin-angiotensin system (RAS) blockers were randomized to a cilnidipine 10 mg treatment (n=38) or amlodipine 5 mg treatment (n=36)...
August 24, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28822969/preconditioning-with-the-bkca-channel-activator-ns-1619-prevents-ischemia-reperfusion-induced-inflammation-and-mucosal-barrier-dysfunction-ros-and-ho-1
#10
Hongyan Dai, Meifang Wang, Parag N Patel, Theodore J Kalogeris, Yajun Liu, William Durante, Ronald J Korthuis
Activation of large conductance, calcium-activated potassium (BKCa) channels evokes cell survival programs that mitigate intestinal ischemia and reperfusion (I/R) inflammation and injury 24 hours later. The goal of the current study was to determine the role of reactive oxygen species (ROS) and heme oxygenase (HO)-1 in delayed acquisition of tolerance to I/R induced by pretreatment with the BKCa channel opener NS-1619. Superior mesentery arteries were occluded for 45 min followed by reperfusion for 70 min in wild type (WT) or HO-1 null (HO-1(-/-)) mice that were pretreated with NS-1619 or saline vehicle 24 hrs earlier...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28815011/genomic-upregulation-of-cardiac-cav1-2%C3%AE-and-ncx1-by-estrogen-in-women
#11
Rita Papp, Glenna C L Bett, Agnieszka Lis, Randall L Rasmusson, István Baczkó, András Varró, Guy Salama
BACKGROUND: Women have a higher risk of lethal arrhythmias than men in long QT syndrome type 2 (LQTS2), but the mechanisms remain uncertain due to the limited availability of healthy control human tissue. We have previously reported that in female rabbits, estrogen increases arrhythmia risk in drug-induced LQTS2 by upregulating L-type Ca(2+) (ICa,L) and sodium-calcium exchange (INCX) currents at the base of the epicardium by a genomic mechanism. This study investigates if the effects of estrogen on rabbit ICa,L and INCX apply to human hearts...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28809766/crispr-cas9-editing-of-nf1-gene-identifies-crmp2-as-a-therapeutic-target-in-neurofibromatosis-type-1-nf1-related-pain-that-is-reversed-by-s-lacosamide
#12
Aubin Moutal, Xiaofang Yang, Wennan Li, Kerry B Gilbraith, Shizhen Luo, Song Cai, Liberty François-Moutal, Lindsey A Chew, Seul Ki Yeon, Shreya S Bellampalli, Chaoling Qu, Jennifer Y Xie, Mohab M Ibrahim, May Khanna, Ki Duk Park, Frank Porreca, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. NF1 patients commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by NF1 patients. However, behavioral assessments of Nf1+/- mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats/(CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain...
July 3, 2017: Pain
https://www.readbyqxmd.com/read/28807015/genomic-upregulation-of-cardiac-cav1-2%C3%AE-and-ncx1-by-estrogen-in-women
#13
Rita Papp, Glenna C L Bett, Agnieszka Lis, Randall L Rasmusson, István Baczkó, András Varró, Guy Salama
BACKGROUND: Women have a higher risk of lethal arrhythmias than men in long QT syndrome type 2 (LQTS2), but the mechanisms remain uncertain due to the limited availability of healthy control human tissue. We have previously reported that in female rabbits, estrogen increases arrhythmia risk in drug-induced LQTS2 by upregulating L-type Ca(2+) (ICa,L) and sodium-calcium exchange (INCX) currents at the base of the epicardium by a genomic mechanism. This study investigates if the effects of estrogen on rabbit ICa,L and INCX apply to human hearts...
August 14, 2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28790888/amyloid-%C3%AE-1-42-a%C3%AE-1-42-induces-the-cdk2-mediated-phosphorylation-of-tau-through-the-activation-of-the-mtorc1-signaling-pathway-while-promoting-neuronal-cell-death
#14
Ki Hoon Lee, Sei-Jung Lee, Hyun Jik Lee, Gee Euhn Choi, Young Hyun Jung, Dah Ihm Kim, Amr Ahmed Gabr, Jung Min Ryu, Ho Jae Han
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by cognitive impairment and memory loss. Amyloid β1-42 (Aβ) and hyper-phosphorylation of microtubule-associated protein tau have been considered as major histological features in AD. However, the mechanism of how Aβ induces the hyper-phosphorylation of tau remains to be clarified. In the present study, we investigated the underlying cellular mechanisms of Aβ with regard to the cell cycle regulatory protein-mediated phosphorylation of tau in promoting neuronal cell death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28767512/dissecting-the-role-of-the-crmp2-neurofibromin-complex-on-pain-behaviors
#15
Aubin Moutal, Yue Wang, Xiaofang Yang, Yingshi Ji, Shizhen Luo, Angie Dorame, Shreya S Bellampalli, Lindsey A Chew, Song Cai, Erik T Dustrude, James E Keener, Michael T Marty, Todd W Vanderah, Rajesh Khanna
Neurofibromatosis type 1 (NF1), a genetic disorder linked to inactivating mutations or homozygous deletion of the Nf1 gene, is characterized by tumorigenesis, cognitive dysfunction, seizures, migraine, and pain. Omic studies on human NF1 tissues identified an increase in expression of collapsin response mediator protein 2 (CRMP2), a cytosolic protein reported to regulate the trafficking and activity of presynaptic N-type voltage-gated calcium (Cav2.2) channels. Since neurofibromin, the protein product of the Nf1 gene, binds to and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect Ca2+ channel activity and regulate nociceptive neurotransmission and in vivo responses to noxious stimulation...
July 31, 2017: Pain
https://www.readbyqxmd.com/read/28760939/visit-to-visit-office-blood-pressure-variability-and-cardiovascular-outcomes-in-sprint-systolic-blood-pressure-intervention-trial
#16
Tara I Chang, David M Reboussin, Glenn M Chertow, Alfred K Cheung, William C Cushman, William J Kostis, Gianfranco Parati, Dominic Raj, Erik Riessen, Brian Shapiro, George S Stergiou, Raymond R Townsend, Konstantinos Tsioufis, Paul K Whelton, Jeffrey Whittle, Jackson T Wright, Vasilios Papademetriou
Studies of visit-to-visit office blood pressure (BP) variability (OBPV) as a predictor of cardiovascular events and death in high-risk patients treated to lower BP targets are lacking. We conducted a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a well-characterized cohort of participants randomized to intensive (<120 mm Hg) or standard (<140 mm Hg) systolic BP targets. We defined OBPV as the coefficient of variation of the systolic BP using measurements taken during the 3-,6-, 9-, and 12-month study visits...
July 31, 2017: Hypertension
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
#17
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
#18
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
#19
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
#20
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...
August 2017: British Journal of Pharmacology
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