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T-type calcium channel

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https://www.readbyqxmd.com/read/28800734/a-t-type-channel-calmodulin-complex-triggers-%C3%AE-camkii-activation
#1
Hadhimulya Asmara, Ileana Micu, Arsalan P Rizwan, Giriraj Sahu, Brett A Simms, Fang-Xiong Zhang, Jordan D T Engbers, Peter K Stys, Gerald W Zamponi, Ray W Turner
Calmodulin (CaM) is an important signaling molecule that regulates a vast array of cellular functions by activating second messengers involved in cell function and plasticity. Low voltage-activated calcium channels of the Cav3 family have the important role of mediating low threshold calcium influx, but were not believed to interact with CaM. We find a constitutive association between CaM and the Cav3.1 channel at rest that is lost through an activity-dependent and Cav3.1 calcium-dependent CaM dissociation...
August 11, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28777254/t-type-and-l-type-calcium-channel-blockers-for-the-treatment-of-cardiac-iron-overload-an-update
#2
Sirinart Kumfu, Siriporn C Chattipakorn, Nipon Chattipakorn
In thalassemia patients iron overload cardiomyopathy is a major cause of cardiac dysfunction and mortality. Despite many advances in the development of new iron chelating agents, heart failure still occurs in some patients and can lead to an increase in mortality rate. Recently, potential novel therapeutic strategies in the treatment of these patients have focused on L-type and T-type calcium channel blockers. These two channels have been reported as being the main routes for cardiac iron uptake under conditions of iron overload...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28767512/dissecting-the-role-of-the-crmp2-neurofibromin-complex-on-pain-behaviors
#3
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
#4
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/28751716/static-magnetic-field-stimulation-enhances-oligodendrocyte-differentiation-and-secretion-of-neurotrophic-factors
#5
Ankshita Prasad, Daniel B Loong Teh, Agata Blasiak, Chou Chai, Yang Wu, Payam M Gharibani, In Hong Yang, Thang T Phan, Kah Leong Lim, Hyunsoo Yang, Xiaogang Liu, Angelo H All
The cellular-level effects of low/high frequency oscillating magnetic field on excitable cells such as neurons are well established. In contrast, the effects of a homogeneous, static magnetic field (SMF) on Central Nervous System (CNS) glial cells are less investigated. Here, we have developed an in vitro SMF stimulation set-up to investigate the genomic effects of SMF exposure on oligodendrocyte differentiation and neurotrophic factors secretion. Human oligodendrocytes precursor cells (OPCs) were stimulated with moderate intensity SMF (0...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28749367/genome-wide-association-study-of-susceptibility-to-particulate-matter-associated-qt-prolongation
#6
Rahul Gondalia, Christy L Avery, Melanie D Napier, Raúl Méndez-Giráldez, James D Stewart, Colleen M Sitlani, Yun Li, Kirk C Wilhelmsen, Qing Duan, Jeffrey Roach, Kari E North, Alexander P Reiner, Zhu-Ming Zhang, Lesley F Tinker, Jeff D Yanosky, Duanping Liao, Eric A Whitsel
BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). METHODS: Using repeated electrocardiograms (1986-2004), longitudinal data on in diameter (), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately interactions among nine Women's Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (), then combined subpopulation-specific results in a fixed-effects, inverse variance-weighted meta-analysis...
June 8, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28744923/the-role-of-t-type-calcium-channels-in-the-subiculum-to-burst-or-not-to-burst
#7
Srdjan M Joksimovic, Pierce Eggan, Yukitoshi Izumi, Sonja Lj Joksimovic, Vesna Tesic, Robert M Dietz, James E Orfila, Michael R DiGruccio, Paco S Herson, Vesna Jevtovic-Todorovic, Charles F Zorumski, Slobodan M Todorovic
Several studies suggest that voltage-gated calcium currents are involved in generating high frequency burst firing in the subiculum, but the exact nature of these currents remains unknown. Here, we used selective pharmacology, molecular and genetic approaches to implicate Cav3.1-containing T-channels in subicular burst firing, in contrast to several previous reports discounting T-channels as major contributors to subicular neuron physiology. Furthermore, pharmacological antagonism of T-channels completely suppressed development of long-term potentiation (LTP) in the CA1-subiculum, but not in the CA3-CA1 pathway...
July 26, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28742985/gabab-receptors-suppress-burst-firing-in-reticular-thalamic-neurons
#8
Stuart M Cain, Esperanza Garcia, Zeina Waheed, Karen L Jones, Trevor J Bushell, Terrance P Snutch
Burst-firing in thalamic neurons is known to play a key role in mediating thalamocortical (TC) oscillations that are associated with non-REM sleep and some types of epileptic seizure. Within the TC system the primary output of GABAergic neurons in the reticular thalamic nucleus (RTN) is thought to induce the de-inactivation of T-type calcium channels in thalamic relay (TR) neurons, promoting burst-firing drive to the cortex and the propagation of TC network activity. However, RTN neurons also project back onto other neurons within the RTN...
July 25, 2017: Channels
https://www.readbyqxmd.com/read/28720792/optical-read-out-of-neural-activity-in-mammalian-peripheral-axons-calcium-signaling-at-nodes-of-ranvier
#9
Arjun K Fontaine, Emily A Gibson, John H Caldwell, Richard F Weir
Current neural interface technologies have serious limitations for advanced prosthetic and therapeutic applications due primarily to their lack of specificity in neural communication. An optogenetic approach has the potential to provide single cell/axon resolution in a minimally invasive manner by optical interrogation of light-sensitive reporters and actuators. Given the aim of reading neural activity in the peripheral nervous system, this work has investigated an activity-dependent signaling mechanism in the peripheral nerve...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720332/synthesis-and-biological-evaluation-of-fluoro-substituted-3-4-dihydroquinazoline-derivatives-for-cytotoxic-and-analgesic-effects
#10
Jin Han Kim, Hui Rak Jeong, Da Woon Jung, Hong Bin Yoon, Sun Young Kim, Hyoung Ja Kim, Kyung-Tae Lee, Vinicius M Gadotti, Junting Huang, Fang-Xiong Zhang, Gerald W Zamponi, Jae Yeol Lee
As a bioisosteric strategy to overcome the poor metabolic stability of lead compound KYS05090S, a series of new fluoro-substituted 3,4-dihydroquinazoline derivatives was prepared and evaluated for T-type calcium channel (Cav3.2) block, cytotoxic effects and liver microsomal stability. Among them, compound 8h (KCP10068F) containing 4-fluorobenzyl amide and 4-cyclohexylphenyl ring potently blocked Cav3.2 currents (>90% inhibition) at 10μM concentration and exhibited cytotoxic effect (IC50=5.9μM) in A549 non-small cell lung cancer cells that was comparable to KYS05090S...
July 8, 2017: Bioorganic & Medicinal Chemistry
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
#11
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/28701796/camk-ii-%C3%AE-down-regulation-protects-dorsal-root-ganglion-neurons-from-ropivacaine-hydrochloride-neurotoxicity
#12
Xian-Jie Wen, Xiao-Hong Li, Heng Li, Hua Liang, Chen-Xiang Yang, Han-Bing Wang
T-type calcium channels are intimately involved in the local anesthetics neurotoxicity. Does CaMKIIγ regulate T-type calcium currents in local anesthetics neurotoxicity? This study generated pAd-CaMKIIγ and pAd-shRNA adenovirus vectors to up- and down-regulate CaMKIIγ mRNA expression in dorsal root ganglion neurons (DRG). Normal DRG (Normal group), empty vector DRG (Empty vector group), pAd-CaMKIIγ DRG (pAd-CaMKIIγ group) and pAd-shRNA DRG (pAd-shRNA group) were treated or untreated with 3 mM ropivacaine hydrochloride for 4 h...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697281/transport-of-the-alpha-subunit-of-the-l-type-calcium-channel-through-the-sarcoplasmic-reticulum-occurs-prior-to-localization-to-triads-and-requires-the-beta-subunit-but-not-stac3-in-skeletal-muscles
#13
Jeremy W Linsley, I-Uen Hsu, Wenjai Wang, John Y Kuwada
Contraction of skeletal muscle is initiated by excitation-contraction (EC) coupling during which membrane voltage is transduced to intracellular Ca(2+) release. EC coupling requires dihydropyridine receptors (DHPR) located at triads, which are junctions between the transverse (T) tubule and SR membranes, that sense membrane depolarization in the T tubule membrane. Reduced EC coupling is associated with ageing, and disruptions of EC coupling result in congenital myopathies for which there are few therapies. The precise localization of DHPRs to triads is critical for EC coupling, yet trafficking of the DHPR to triads is not well understood...
July 11, 2017: Traffic
https://www.readbyqxmd.com/read/28696432/cross-disorder-risk-gene-cacna1c-differentially-modulates-susceptibility-to-psychiatric-disorders-during-development-and-adulthood
#14
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/28693898/nanosecond-pulsed-electric-fields-depolarize-transmembrane-potential-via-voltage-gated-k-ca-2-and-trpm8-channels-in-u87-glioblastoma-cells
#15
Ryan C Burke, Sylvia M Bardet, Lynn Carr, Sergii Romanenko, Delia Arnaud-Cormos, Philippe Leveque, Rodney P O'Connor
Nanosecond pulsed electric fields (nsPEFs) have a variety of applications in the biomedical and biotechnology industries. Cancer treatment has been at the forefront of investigations thus far as nsPEFs permeabilize cellular and intracellular membranes leading to apoptosis and necrosis. nsPEFs may also influence ion channel gating and have the potential to modulate cell physiology without poration of the membrane. This phenomenon was explored using live cell imaging and a sensitive fluorescent probe of transmembrane voltage in the human glioblastoma cell line, U87 MG, known to express a number of voltage-gated ion channels...
July 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28673569/calcium-channel-blockers-as-therapeutic-agents-for-acquired-sensorineural-hearing-loss
#16
James G Naples
Acquired sensorineural hearing loss represents a challenging clinical scenario. Currently, there are few approved therapies for treating this type of hearing loss, and diagnosis is often made after permanent damage has occurred. There are numerous etiologies for acquired hearing loss, with complex mechanisms underlying each cause. Despite these complexities, apoptosis of the structures within the inner ear, is a theme common to many forms of acquired hearing loss. Apoptosis is a calcium-dependent process, and within the inner ear, L- and T-type calcium channels are believed to contribute to calcium availability during this process...
July 2017: Medical Hypotheses
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
#17
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/28658605/sociability-impairments-in-genetic-absence-epilepsy-rats-from-strasbourg-reversal-by-the-t-type-calcium-channel-antagonist-z944
#18
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/28648030/-effect-and-mechanism-of-intermittent-alkaline-stimulation-on-high-phosphorus-induced-calcification-in-vascular-smooth-muscle-cells-of-rats
#19
Y L Bai, J S Xu, T Tian, J X Zhang, L W Cui, H R Zhang, S L Zhang
Objective: To explore the effect and possible mechanisms of intermittent alkaline on rat vascular smooth muscle cells (VSMCs) calcification induced by high phosphorus. Methods: VSMCs were isolated from rat thoracic aorta and cultured in vitro. The fourth generation VSMCs were randomly divided into control group, high phosphorus+ pH7.4, high phosphorus+ pH7.5, high phosphorus+ pH7.6 and high phosphorus+ pH7.7 group with random number table. The control group was cultured in DMEM with 10% fetal bovine serum. Other groups were cultured in DMEM with 10 mmol/L β-glycerophosphate and alkalized by 7...
June 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28637420/bioinformatics-insights-on-targets-receptors-of-amiodarone-in-human-and-acanthamoeba-castellanii
#20
Abdul Baig, Zohaib Rana, H R Ahmad
BACKGROUND: Amiodarone is prescribed for certain cardiac arrhythmias in medical practice. The drug targets and inhibits voltage dependent sodium (Na+v), calcium (Ca+2v), potassium (K+v) channels, and enzymes like cytochrome P450 and oxidosqualene cyclase. Past studies have shown that amiodarone exerts anti-amoebic effects against Trypanosoma cruzi and Acanthamoeba castellanii. OBJECTIVES: The presence of aforementioned targets and the type of cell death induced by amiodarone in these pathogenic eukaryotes like Acanthamoeba castellanii remain to be verified...
June 21, 2017: Infectious Disorders Drug Targets
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