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T type calcium channel

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https://www.readbyqxmd.com/read/29773754/a-critical-neurodevelopmental-role-for-l-type-voltage-gated-calcium-channels-in-neurite-extension-and-radial-migration
#1
Satoshi Kamijo, Yuichiro Ishii, Shin-Ichiro Horigane, Kanzo Suzuki, Masamichi Ohkura, Junichi Nakai, Hajime Fujii, Sayaka Takemoto-Kimura, Haruhiko Bito
In spite of many association studies linking gene polymorphisms and mutations of L-type Voltage-Gated Ca2+ Channels (VGCC) in neurodevelopmental disorders, such as autism and schizophrenia, specific L-type VGCC roles during brain development remain unclear. Yet, calcium signaling has been shown to be essential for neurodevelopmental processes such as sculpting of neurites, functional wiring and fine tuning of growing networks. To bridge this gap, we performed submembraneous calcium imaging using a membrane-tethered genetically-encoded calcium indicator (GECI) Lck-G-CaMP7...
May 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29755321/voltage-gated-calcium-channel-activation-by-backpropagating-action-potentials-downregulates-nmdar-function
#2
Anne-Kathrin Theis, Balázs Rózsa, Gergely Katona, Dietmar Schmitz, Friedrich W Johenning
The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs) propagate back into the dendritic tree and activate voltage gated Ca2+ channels (VGCCs). For spines, this global mode of spine Ca2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs) result in long-term enhancement of spine VGCCs...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29748130/effects-of-the-iron-chelator-deferiprone-and-the-t-type-calcium-channel-blocker-efonidipine-on-cardiac-function-and-ca-2-regulation-in-iron-overloaded-thalassemic-mice
#3
Juthamas Khamseekaew, Sirinart Kumfu, Siripong Palee, Suwakon Wongjaikam, Somdet Srichairatanakool, Suthat Fucharoen, Siriporn C Chattipakorn, Nipon Chattipakorn
Although disturbance of cardiac Ca2+ regulation is involved in the pathophysiology of iron-overload cardiomyopathy, the obvious mechanisms involved in the dysregulation of iron-induced cardiac Ca2+ are unclear. Moreover, the roles of the iron chelator deferiprone and the T-type calcium channel blocker efonidipine on cardiac intracellular Ca2+ transients and Ca2+ regulatory proteins in thalassemic mice are still unknown. We tested the hypothesis that treatment with either deferiprone or efonidipine attenuated cardiac Ca2+ dysregulation and led to improved left ventricular (LV) function in iron-overloaded thalassemic mice...
February 6, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29746088/structure-activity-studies-reveal-the-molecular-basis-for-gabab-receptor-mediated-inhibition-of-high-voltage-activated-calcium-channels-by-%C3%AE-conotoxin-vc1-1
#4
Mahsa Sadeghi, Bodil B Carstens, Brid P Callaghan, James T Daniel, Han Shen Tae, Tracey O'Donnell, Joel Castro, Stuart M Brierley, David J Adams, David J Craik, Richard J Clark
α-Conotoxins are disulfide-bonded peptides from cone snail venoms and are characterized by their affinity for nicotinic acetylcholine receptors (nAChR). Several α-conotoxins with distinct selectivity for nAChR subtypes have been identified as potent analgesics in animal models of chronic pain. However, a number of α-conotoxins have been shown to inhibit N-type calcium channel currents in rodent dissociated dorsal root ganglion (DRG) neurons via activation of G protein-coupled GABAB receptors (GABABR). Therefore it is unclear whether activation of GABABR or inhibition of α9α10 nAChRs is the analgesic mechanism...
May 10, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29745425/arrhythmic-hazard-map-for-a-3d-whole-ventricles-model-under-multiple-ion-channel-block
#5
Jun-Ichi Okada, Takashi Yoshinaga, Junko Kurokawa, Takumi Washio, Tetsushi Furukawa, Kohei Sawada, Seiryo Sugiura, Toshiaki Hisada
BACKGROUND AND PURPOSE: To date, proposed in silico models for preclinical cardiac safety testing are limited in their predictability and usability. We previously reported a multi-scale heart simulation that accurately predicts arrhythmogenic risk for benchmark drugs. EXPERIMENTAL APPROACH: We extend this approach and report the first comprehensive hazard map of drug-induced arrhythmia based on the exhaustive in silico electrocardiogram (ECG) database of drug effects, developed using a petaflop computer...
May 10, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29739832/expression-of-calcium-channel-transcripts-in-the-zebrafish-heart-dominance-of-t-type-channels
#6
Jaakko Haverinen, Minna Hassinen, Surjya Narayan Dash, Matti Vornanen
Calcium (Ca) channels are necessary for cardiac excitation-contraction (e-c) coupling, but Ca channel composition of fish hearts is still largely unknown. To this end, we determined transcript expression of Ca channels in the heart of zebrafish ( Danio rerio ), a popular model species. Altogether 18 Ca channel α-subunit genes were expressed in both atrium and ventricle. Transcripts for 7 L-type (Cav1.1a, Cav1.1b, Cav1.2, Cav1.3a, Cav1.3b, Cav1.4a, Cav1.4b), 5 T-type (Cav3.1, Cav3.2a, Cav3.2b, Cav3.3a, Cav3...
May 8, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29720608/drosophila-voltage-gated-calcium-channel-%C3%AE-1-subunits-regulate-cardiac-function-in-the-aging-heart
#7
Alexander Lam, Priyanka Karekar, Kajol Shah, Girija Hariharan, Michelle Fleyshman, Harmehak Kaur, Harpreet Singh, Shubha Gururaja Rao
Ion channels maintain numerous physiological functions and regulate signaling pathways. They are the key targets for cellular reactive oxygen species (ROS), acting as signaling switches between ROS and ionic homeostasis. We have carried out a paraquat (PQ) screen in Drosophila to identify ion channels regulating the ROS handling and survival in Drosophila melanogaster. Our screen has revealed that α1-subunits (D-type, T-type, and cacophony) of voltage-gated calcium channels (VGCCs) handle PQ-mediated ROS stress differentially in a gender-based manner...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29720258/t-type-calcium-channels-functionally-interact-with-spectrin-%C3%AE-%C3%AE-and-ankyrin-b
#8
Agustin Garcia-Caballero, Fang-Xiong Zhang, Victoria Hodgkinson, Junting Huang, Lina Chen, Ivana A Souza, Stuart Cain, Jennifer Kass, Sascha Alles, Terrance P Snutch, Gerald W Zamponi
This study describes the functional interaction between the Cav3.1 and Cav3.2 T-type calcium channels and cytoskeletal spectrin (α/β) and ankyrin B proteins. The interactions were identified utilizing a proteomic approach to identify proteins that interact with a conserved negatively charged cytosolic region present in the carboxy-terminus of T-type calcium channels. Deletion of this stretch of amino acids decreased binding of Cav3.1 and Cav3.2 calcium channels to spectrin (α/β) and ankyrin B and notably also reduced T-type whole cell current densities in expression systems...
May 2, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29705290/investigation-of-the-role-of-ion-channels-in-human-pancreatic-%C3%AE-cell-hubs-a-mathematical-modeling-study
#9
Sajjad Farashi, Pezhman Sasanpour, Hashem Rafii-Tabar
In many cellular networks, the structure of the network follows a scale-free organization, where a limited number of cells are strongly coupled to other cells. These cells are called hub cells and their critical roles are well accepted. Despite their importance, there have been only a few studies investigating the characteristic features of these cells. In this paper, a computational approach is proposed to study the possible role of different ion channels in distinguishing between the hub and non-hub cells...
April 12, 2018: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/29704319/a-molecule-based-genetic-association-approach-implicates-a-range-of-voltage-gated-calcium-channels-associated-with-schizophrenia
#10
Wen Li, Chun Chieh Fan, Tuomo Mäki-Marttunen, Wesley K Thompson, Andrew J Schork, Francesco Bettella, Srdjan Djurovic, Anders M Dale, Ole A Andreassen, Yunpeng Wang
Traditional genome-wide association studies (GWAS) have successfully detected genetic variants associated with schizophrenia. However, only a small fraction of heritability can be explained. Gene-set/pathway-based methods can overcome limitations arising from single nucleotide polymorphism (SNP)-based analysis, but most of them place constraints on size which may exclude highly specific and functional sets, like macromolecules. Voltage-gated calcium (Cav ) channels, belonging to macromolecules, are composed of several subunits whose encoding genes are located far away or even on different chromosomes...
April 28, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/29684576/zd7288-and-mibefradil-inhibit-the-myogenic-heartbeat-in-daphnia-magna-indicating-its-dependency-on-hcn-and-t-type-calcium-ion-channels
#11
Thomas J Pirtle, Troy L Carr, Tanisha Khurana, Grace Meeker
Daphnia magna heartbeat is myogenic-originating within the animal's heart. However, the mechanism for this myogenic automaticity is unknown. The mechanism underlying the automaticity of vertebrate myogenic hearts involves cells (pacemaker cells), which have a distinct set of ion channels that include hyperpolarization activated cyclic nucleotide-gated (HCN) and T-type calcium ion channels. We hypothesized that these ion channels also underlie the automatic myogenic heartbeat of Daphnia magna. The drugs, ZD7288 and mibefradil dihydrochloride, block HCN and T-type calcium ion channels respectively...
April 20, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29684385/upregulation-of-ca-v-3-2-t-type-calcium-channels-in-adjacent-intact-l4-dorsal-root-ganglion-neurons-in-neuropathic-pain-rats-with-l5-spinal-nerve-ligation
#12
Qing-Ying Liu, Wen Chen, Shuang Cui, Fei-Fei Liao, Ming Yi, Feng-Yu Liu, You Wan
Besides the injured peripheral dorsal root ganglion (DRG) neurons, the adjacent intact DRG neurons also have important roles in neuropathic pain. Ion channels including Cav 3.2 T-type calcium channel in the DRG neurons are important in the development of neuropathic pain. In the present study, we aimed to examine the expression of Cav 3.2 T-type calcium channels in the intact DRG neurons in neuropathic pain. A neuropathic pain model of rat with lumbar 5 (L5) spinal nerve ligation (SNL) was established, in which the L4 DRG was separated from the axotomized L5 DRG, and the molecular, morphological and electrophysiological changes of Cav 3...
April 20, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29684009/switchable-slow-cellular-conductances-determine-robustness-and-tunability-of-network-states
#13
Guillaume Drion, Julie Dethier, Alessio Franci, Rodolphe Sepulchre
Neuronal information processing is regulated by fast and localized fluctuations of brain states. Brain states reliably switch between distinct spatiotemporal signatures at a network scale even though they are composed of heterogeneous and variable rhythms at a cellular scale. We investigated the mechanisms of this network control in a conductance-based population model that reliably switches between active and oscillatory mean-fields. Robust control of the mean-field properties relies critically on a switchable negative intrinsic conductance at the cellular level...
April 23, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29675595/involvement-of-cytosolic-and-mitochondrial-iron-in-iron-overload-cardiomyopathy-an-update
#14
REVIEW
Richard Gordan, Suwakon Wongjaikam, Judith K Gwathmey, Nipon Chattipakorn, Siriporn C Chattipakorn, Lai-Hua Xie
Iron overload cardiomyopathy (IOC) is a major cause of death in patients with diseases associated with chronic anemia such as thalassemia or sickle cell disease after chronic blood transfusions. Associated with iron overload conditions, there is excess free iron that enters cardiomyocytes through both L- and T-type calcium channels thereby resulting in increased reactive oxygen species being generated via Haber-Weiss and Fenton reactions. It is thought that an increase in reactive oxygen species contributes to high morbidity and mortality rates...
April 19, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29668007/a-concise-total-synthesis-of-cochlearoid-b
#15
Wuxia Zhang, Dehai Xiao, Bo Wang
A T-type calcium channel inhibiting natural product cochlearoid B was synthesized for the first time in 7 linear steps via a convergent strategy exploiting the Suzuki-Miyaura cross coupling and the acid promoted Prins cyclization cascade. This strategy allows rapid access to its structural analogues for further therapeutical development.
April 18, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29667130/beneficial-effects-of-the-calcium-channel-blocker-ctk-01512-2-in-a-mouse-model-of-multiple-sclerosis
#16
Rodrigo B M Silva, Samuel Greggio, Gianina T Venturin, Jaderson C da Costa, Marcus V Gomez, Maria M Campos
Voltage-gated calcium channels (VGCCs) play a critical role in neuroinflammatory diseases, such as multiple sclerosis (MS). CTK 01512-2 is a recombinant version of the peptide Phα1β derived from the spider Phoneutria nigriventer, which inhibits N-type VGCC/TRPA1-mediated calcium influx. We investigated the effects of this molecule in the mouse model of experimental autoimmune encephalomyelitis (EAE). The effects of CTK 01512-2 were compared to those displayed by ziconotide-a selective N-type VGCC blocker clinically used for chronic pain-and fingolimod-a drug employed for MS treatment...
April 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29649319/unraveling-endothelin-1-induced-hypercontractility-of-human-pulmonary-artery-smooth-muscle-cells-from-patients-with-pulmonary-arterial-hypertension
#17
Jamie L Wilson, Rod Warburton, Linda Taylor, Deniz Toksoz, Nicholas Hill, Peter Polgar
Contraction of human pulmonary artery smooth muscle cells (HPASMC) isolated from pulmonary arterial hypertensive (PAH) and normal (non-PAH) subject lungs was determined and measured with real-time electrical impedance. Treatment of HPASMC with vasoactive peptides, endothelin-1 (ET-1) and bradykinin (BK) but not angiotensin II, induced a temporal decrease in the electrical impedance profile mirroring constrictive morphological change of the cells which typically was more robust in PAH as opposed to non-PAH cells...
2018: PloS One
https://www.readbyqxmd.com/read/29626474/canstatin-modulates-l-type-calcium-channel-activity-in-rat-ventricular-cardiomyocytes
#18
Keisuke Imoto, Masaki Hirakawa, Muneyoshi Okada, Hideyuki Yamawaki
Excessive increase of cytosolic Ca2+ through the activation of L-type Ca2+ channels (LTCCs) via β adrenergic receptor induces apoptosis of cardiomyocytes. Canstatin, a cleaved fragment of collagen type IV α2 chain, is abundantly expressed in normal heart tissue. We previously reported that canstatin inhibits β adrenergic receptor-stimulated apoptosis in cardiomyoblasts. Here, we tested the hyposeis that canstatin regulates LTCCs activity in ventricular cardiomyocytes. Collagen type IV α2 chain (COL4A2) small interfering (si) RNA (for canstatin suppression) or control siRNA was injected via jugular vein in Wistar rats...
April 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29622412/synthesis-and-evaluation-of-aminobenzothiazoles-as-blockers-of-n-and-t-type-calcium-channels
#19
Anjali Sairaman, Fernanda Caldas Cardoso, Anjie Bispat, Richard J Lewis, Peter J Duggan, Kellie L Tuck
Both N- and T-type calcium ion channels have been implicated in pain transmission and the N-type channel is a well-validated target for the treatment of neuropathic pain. An SAR investigation of a series of substituted aminobenzothiazoles identified a subset of five compounds with comparable activity to the positive control Z160 in a FLIPR-based intracellular calcium response assay measuring potency at both CaV 2.2 and CaV 3.2 channels. These compounds may form the basis for the development of drug leads and tool compounds for assessing in vivo effects of variable modulation of CaV 2...
March 19, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29603093/oxaliplatin-modulates-the-characteristics-of-voltage-gated-calcium-channels-and-action-potentials-in-small-dorsal-root-ganglion-neurons-of-rats
#20
Linda-Isabell Schmitt, Markus Leo, Christoph Kleinschnitz, Tim Hagenacker
Oxaliplatin is important for treating colorectal cancer. Although oxaliplatin is highly effective, it has severe side effects, of which neurotoxicity in dorsal root ganglion (DRG) neurons is one of the most common. The key mechanisms of this neurotoxicity are still controversial. However, disturbances of calcium homeostasis in DRG neurons have been suggested to mediate oxaliplatin neurotoxicity. By using whole-cell patch-clamp and current-clamp techniques, as well as immunocytochemical staining, we examined the influence of short- and long-term exposure to oxaliplatin on voltage-gated calcium channels (VGCC) and different VGCC subtypes in small DRG neurons of rats in vitro...
March 30, 2018: Molecular Neurobiology
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