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N-type calcium channels

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https://www.readbyqxmd.com/read/28330839/evolutionary-insights-into-t-type-ca-2-channel-structure-function-and-ion-selectivity-from-the-trichoplax-adhaerens-homologue
#1
Carolyn L Smith, Salsabil Abdallah, Yuen Yan Wong, Phuong Le, Alicia N Harracksingh, Liana Artinian, Arianna N Tamvacakis, Vincent Rehder, Thomas S Reese, Adriano Senatore
Four-domain voltage-gated Ca(2+) (Cav) channels play fundamental roles in the nervous system, but little is known about when or how their unique properties and cellular roles evolved. Of the three types of metazoan Cav channels, Cav1 (L-type), Cav2 (P/Q-, N- and R-type) and Cav3 (T-type), Cav3 channels are optimized for regulating cellular excitability because of their fast kinetics and low activation voltages. These same properties permit Cav3 channels to drive low-threshold exocytosis in select neurons and neurosecretory cells...
March 22, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28322832/dapoxetine-induces-neuroprotective-effects-against-glutamate-induced-neuronal-cell-death-by-inhibiting-calcium-signaling-and-mitochondrial-depolarization-in-cultured-rat-hippocampal-neurons
#2
Imju Jeong, Ji Seon Yang, Yi Jae Hong, Hee Jung Kim, Sang June Hahn, Shin Hee Yoon
Selective serotonin reuptake inhibitors (SSRIs) have an inhibitory effect on various ion channels including Ca(2+) channels. We used fluorescent dye-based digital imaging, whole-cell patch clamping and cytotoxicity assays to examine whether dapoxetine, a novel rapid-acting SSRI, affect glutamate-induced calcium signaling, mitochondrial depolarization and neuronal cell death in cultured rat hippocampal neurons. Pretreatment with dapoxetine for 10min inhibited glutamate-induced intracellular free Ca(2+) concentration ([Ca(2+)]i) increases in a concentration-dependent manner (Half maximal inhibitory concentration= 4...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28315276/the-sigma-1-receptor-a-therapeutic-target-for-the-treatment-of-als
#3
Timur A Mavlyutov, Erin M Baker, Tasher M Losenegger, Jaimie R Kim, Brian Torres, Miles L Epstein, Arnold E Ruoho
The membrane bound 223 amino acid Sigma-1 Receptor (S1R) serves as a molecular chaperone and functional regulator of many signaling proteins. Spinal cord motor neuron activation occurs, in part, via large ventral horn cholinergic synapses called C-boutons/C-terminals. Chronic excitation of motor neurons and alterations in C-terminals has been associated with Amyotrophic Lateral Sclerosis (ALS ). The S1R has an important role in regulating motor neuron function. High levels of the S1R are localized in postsynaptic endoplasmic reticulum (ER) subsurface cisternae within 10-20 nm of the plasma membrane that contain muscarinic type 2 acetylcholine receptors (M2AChR), calcium activated potassium channels (Kv2...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299825/fingolimod-gilenya-%C3%A2-in-multiple-sclerosis-bradycardia-atrioventricular-blocks-and-mild-effect-on-the-qtc-interval-something-to-do-with-the-l-type-calcium-channel
#4
Sylvie Pilote, Chantale Simard, Benoit Drolet
Cardiac arrhythmias and ECG abnormalities including bradycardia, prolongation of the QT interval and atrioventricular (AV) conduction blocks have been extensively observed with fingolimod, the first marketed oral drug for treating the relapsing-remitting form of multiple sclerosis. The present study was aiming to further elucidate the effects of fingolimod on cardiac electrophysiology at three different levels; 1) in vitro, 2) ex vivo and 3) in vivo. 1) Patch-clamp experiments in whole cell configuration were performed on Cav 1...
March 16, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28290248/the-%C3%AE-2%C3%AE-subunit-and-absence-epilepsy-beyond-calcium-channels
#5
Roberta Celli, Ines Santolini, Michela Guiducci, Gilles van Luijtelaar, Pasquale Parisi, Pasquale Striano, Roberto Gradini, Giuseppe Battaglia, Richard T Ngomba, Ferdinando Nicoletti
Spike-wave discharges, underlying absence seizures, are generated within a cortico-thalamo-cortical network that involves the somatosensory cortex, the reticular thalamic nucleus, and the ventrobasal thalamic nuclei. Activation of T-type voltage-sensitive calcium channels (VSCCs) contributes to the pathological oscillatory activity of this network, and some of the first-line drugs used in the treatment of absence epilepsy inhibit T-type calcium channels. The α2δ subunit is a component of high voltage-activated VSCCs (i...
March 8, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28287621/restoring-the-impaired-cardiac-calcium-homeostasis-and-cardiac-function-in-iron-overload-rats-by-the-combined-deferiprone-and-n-acetyl-cysteine
#6
Suwakon Wongjaikam, Sirinart Kumfu, Juthamas Khamseekaew, Siriporn C Chattipakorn, Nipon Chattipakorn
Intracellular calcium [Ca(2+)]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca(2+)]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28256585/lrp1-influences-trafficking-of-n-type-calcium-channels-via-interaction-with-the-auxiliary-%C3%AE-2%C3%AE-1-subunit
#7
Ivan Kadurin, Simon W Rothwell, Beatrice Lana, Manuela Nieto-Rostro, Annette C Dolphin
Voltage-gated Ca(2+) (CaV) channels consist of a pore-forming α1 subunit, which determines the main functional and pharmacological attributes of the channel. The CaV1 and CaV2 channels are associated with auxiliary β- and α2δ-subunits. The molecular mechanisms involved in α2δ subunit trafficking, and the effect of α2δ subunits on trafficking calcium channel complexes remain poorly understood. Here we show that α2δ-1 is a ligand for the Low Density Lipoprotein (LDL) Receptor-related Protein-1 (LRP1), a multifunctional receptor which mediates trafficking of cargoes...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28239561/regulation-of-cardiac-cacnb2-by-microrna-499-potential-role-in-atrial-fibrillation
#8
Tian-You Ling, Xiao-Li Wang, Qiang Chai, Tong Lu, John M Stulak, Lyle D Joyce, Richard C Daly, Kevin L Greason, Li-Qun Wu, Win-Kuang Shen, Yong-Mei Cha, Hon-Chi Lee
The L-type calcium channel (LTCC) is one of the major ion channels that are known to be associated with the electrical remodeling of atrial fibrillation (AF). In AF, there is significant downregulation of the LTCC, but the underlying mechanism for such downregulation is not clear. We have previously reported that microRNA-499 (miR-499) is significantly upregulated in patients with permanent AF and that KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), is a target of miR-499...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28224412/antihypertensive-medication-use-and-risk-of-renal-cell-carcinoma
#9
Joanne S Colt, Jonathan N Hofmann, Kendra Schwartz, Wong-Ho Chow, Barry I Graubard, Faith Davis, Julie Ruterbusch, Sonja Berndt, Mark P Purdue
PURPOSE: Use of antihypertensive medications has been associated with renal cell carcinoma (RCC), but it is unclear whether specific types of medications increase RCC risk independent of the effect of hypertension, or whether the association varies by histologic subtype. To address this question, we analyzed data from a U.S. population-based case-control study of RCC. METHODS: We collected information on participants' use of drugs to treat hypertension, heart problems, weight control, and swelling...
February 21, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28217089/differential-modulation-of-rhythmic-brain-activity-in-healthy-adults-by-a-t-type-calcium-channel-blocker-an-meg-study
#10
Kerry D Walton, Emeline L Maillet, John Garcia, Timothy Cardozo, Isaac Galatzer-Levy, Rodolfo R Llinás
1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28202629/improving-the-in-silico-assessment-of-proarrhythmia-risk-by-combining-herg-human-ether-%C3%A3-go-go-related-gene-channel-drug-binding-kinetics-and-multichannel-pharmacology
#11
Zhihua Li, Sara Dutta, Jiansong Sheng, Phu N Tran, Wendy Wu, Kelly Chang, Thembi Mdluli, David G Strauss, Thomas Colatsky
BACKGROUND: The current proarrhythmia safety testing paradigm, although highly efficient in preventing new torsadogenic drugs from entering the market, has important limitations that can restrict the development and use of valuable new therapeutics. The CiPA (Comprehensive in vitro Proarrhythmia Assay) proposes to overcome these limitations by evaluating drug effects on multiple cardiac ion channels in vitro and using these data in a predictive in silico model of the adult human ventricular myocyte...
February 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28202361/pre-clinical-evaluation-of-voltage-gated-calcium-channel-blockers-derived-from-the-spider-p-%C3%A2-nigriventer-in-glioma-progression
#12
Natália Fontana Nicoletti, Thaís Cristina Erig, Rafael Fernandes Zanin, Marcelo Ricardo Roxo, Nelson Pires Ferreira, Marcus Vinicius Gomez, Fernanda Bueno Morrone, Maria Martha Campos
This study investigated the effects of P/Q- and N-type voltage-gated calcium channel (VGCC) blockers derived from P. nigriventer in glioma progression, by means of in vitro and in vivo experiments. Glioma cells M059J, U-138MG and U-251MG were used to evaluate the antiproliferative effects of P/Q- and N-type VGCC inhibitors PhTx3-3 and Phα1β from P. nigriventer (0.3-100 pM), in comparison to MVIIC and MVIIA from C. magus (0.3-100 pM), respectively. The toxins were also analyzed in a glioma model induced by implantation of GL261 mouse cells...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28202327/synthesis-and-evaluation-of-anticonvulsant-properties-of-new-n-mannich-bases-derived-from-pyrrolidine-2-5-dione-and-its-3-methyl-3-isopropyl-and-3-benzhydryl-analogs
#13
Sabina Rybka, Jolanta Obniska, Anna Rapacz, Barbara Filipek, Paweł Żmudzki
The aim of this paper was to describe the synthesis of a library of 28 new 1,3-substituted pyrrolidine-2,5-dione as potential anticonvulsant agents. The anticonvulsant activity was evaluated using three acute models of seizures in mice (MES-maximal electroshock, scPTZ-subcutaneous pentylenetetrazole, and 6Hz-psychomotor seizure tests). The neurotoxicity was determined by rotarod test. The most promising compound was found to be N-[{morpholin-1-yl}-methyl]-3-benzhydryl-pyrrolidine-2,5-dione (15), as it was active in the MES (ED50=41...
February 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28199072/genetic-risk-score-analysis-in-early-onset-bipolar-disorder
#14
Paul E Croarkin, Joan L Luby, Kelly Cercy, Jennifer R Geske, Marin Veldic, Matthew Simonson, Paramjit T Joshi, Karen Dineen Wagner, John T Walkup, Malik M Nassan, Alfredo B Cuellar-Barboza, Leah Casuto, Susan L McElroy, Peter S Jensen, Mark A Frye, Joanna M Biernacka
OBJECTIVE: In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). METHODS: Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria...
February 14, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28197288/serum-triglyceride-lowering-effect-of-cilnidipine-in-patients-with-essential-hypertension
#15
Prakash Kumar, Arijit Das, Satish Chandra, Manju Gari, U S P Keshri, Kusum Kumari
BACKGROUND: Many epidemiological studies have established the relationship between hypertension and dyslipidemia. Calcium channel blockers (CCBs) are one of the first-line drugs for newly diagnosed patients with essential hypertension. Cilnidipine as a newer CCB acting by blocking both L- and N-type calcium channels possesses additional beneficial effects apart from lowering blood pressure (BP). The aim of this study was to evaluate the effectiveness of cilnidipine in patients with essential hypertension with borderline dyslipidemia and its effects on lipid profile...
October 2016: Cardiology Research
https://www.readbyqxmd.com/read/28197287/effects-of-cilnidipine-on-heart-rate-and-uric-acid-metabolism-in-patients-with-essential-hypertension
#16
Arijit Das, Prakash Kumar, Abha Kumari, Satish Chandra, Manju Gari, Nidhi Singh, Debleena Dey
BACKGROUND: The relation between hypertension and hyperuricemia has been established by epidemiological studies. Calcium channel blockers are one of the first-line drugs for newly diagnosed patients with essential hypertension. Cilnidipine is a new calcium channel blocker acting by blocking both L- and N-type calcium channels. The aim of this study was to compare the effectiveness of amlodipine and cilnidipine in patients with essential hypertension and their effects on heart rate and serum uric acid levels...
October 2016: Cardiology Research
https://www.readbyqxmd.com/read/28195225/a-novel-bk-channel-targeted-peptide-suppresses-sound-evoked-activity-in-the-mouse-inferior-colliculus
#17
L L Scott, E J Brecht, A Philpo, S Iyer, N S Wu, S J Mihic, R W Aldrich, J Pierce, J P Walton
Large conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. Decades of research support an interest in pharmaceutical applications for modulating BK channel function. Here we report a novel BK channel-targeted peptide with functional activity in vitro and in vivo. This 9-amino acid peptide, LS3, has a unique action, suppressing channel gating rather than blocking the pore of heterologously expressed human BK channels. With an IC50 in the high picomolar range, the apparent affinity is higher than known high affinity BK channel toxins...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194001/enhancing-vta-cav1-3-l-type-ca-2-channel-activity-promotes-cocaine-and-mood-related-behaviors-via-overlapping-ampa-receptor-mechanisms-in-the-nucleus-accumbens
#18
A Martínez-Rivera, J Hao, T F Tropea, T P Giordano, M Kosovsky, R C Rice, A Lee, R L Huganir, J Striessnig, N A Addy, S Han, A M Rajadhyaksha
Genetic factors significantly influence susceptibility for substance abuse and mood disorders. Rodent studies have begun to elucidate a role of Cav1.3 L-type Ca(2+) channels in neuropsychiatric-related behaviors, such as addictive and depressive-like behaviors. Human studies have also linked the CACNA1D gene, which codes for the Cav1.3 protein, with bipolar disorder. However, the neurocircuitry and the molecular mechanisms underlying the role of Cav1.3 in neuropsychiatric phenotypes are not well established...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28188357/analgesic-antiallodynic-and-anticonvulsant-activity-of-novel-hybrid-molecules-derived-from-n-benzyl-2-2-5-dioxopyrrolidin-1-yl-propanamide-and-2-2-5-dioxopyrrolidin-1-yl-butanamide-in-animal-models-of-pain-and-epilepsy
#19
Anna Rapacz, Krzysztof Kamiński, Jolanta Obniska, Paulina Koczurkiewicz, Elżbieta Pękala, Barbara Filipek
The purpose of the present study was to examine the analgesic activity of six novel hybrid molecules, which demonstrated in the previous research anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure (scPTZ) tests in mice. The antinociceptive properties were estimated in three models of pain in mice-the hot plate test, the formalin test, and in the oxaliplatin-induced neuropathy. Moreover, extended anticonvulsant studies were carried out and the antiseizure activity was investigated in the 6-Hz test...
February 10, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28179209/administration-of-anabolic-steroid-during-adolescence-induces-long-term-cardiac-hypertrophy-and-increases-susceptibility-to-ischemia-reperfusion-injury-in-adult-wistar-rats
#20
Fernando de Azevedo Cruz Seara, Raiana Andrade Quintanilha Barbosa, Dahienne Ferreira de Oliveira, Diorney Luiz Souza Gran da Silva, Adriana Bastos Carvalho, Andrea Claudia Freitas Ferreira, José Hamilton Matheus Nascimento, Emerson Lopes Olivares
Chronic administration of anabolic androgenic steroids (AAS) in adult rats results in cardiac hypertrophy and increased susceptibility to myocardial ischemia/reperfusion (IR) injury. Molecular analyses demonstrated that hyperactivation of type 1 angiotensin II (AT1) receptor mediates cardiac hypertrophy induced by AAS and also induces down-regulation of myocardial ATP-sensitive potassium channel (KATP), resulting in loss of exercise-induced cardioprotection. Exposure to AAS during adolescence promoted long-term cardiovascular dysfunctions, such as dysautonomia...
February 5, 2017: Journal of Steroid Biochemistry and Molecular Biology
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