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T type calcium channel

Sheng-Jie Shiue, Chi-Hsu Wang, Tao-Yeuan Wang, Yi-Chun Chen, Jen-Kun Cheng
OBJECTIVE: T-type channel (TCC) CaV3.2 plays a pivotal role in pain transmission. In this study, we examined the effects of intrathecal TCC blockers on CaV3.2 expression in a L5/6 spinal nerve ligation (SNL) pain model. The neurotoxicity of TCC blockers were also evaluated. METHODS: Male Sprague-Dawley rats (200-250 g) were used for right L5/6 SNL to induce neuropathic pain. Intrathecal infusion of saline or TCC blockers [mibefradil (0.7 μg/h) or ethosuximide (60 μg/h)] was started after surgery for 7 days...
October 17, 2016: Acta Anaesthesiologica Taiwanica: Official Journal of the Taiwan Society of Anesthesiologists
Rajeev B Tajhya, Xueyou Hu, Mark R Tanner, Redwan Huq, Natee Kongchan, Joel R Neilson, George G Rodney, Frank T Horrigan, Lubov T Timchenko, Christine Beeton
Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1...
October 20, 2016: Cell Death & Disease
Lubica Lacinova, Norbert Weiss
No abstract text is available yet for this article.
October 2016: General Physiology and Biophysics
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
A Andrade, J Hope, A Allen, V Yorgan, D Lipscombe, J Q Pan
CACNA1I is a candidate schizophrenia risk gene. It encodes the pore-forming human CaV3.3 α1 subunit, a subtype of voltage-gated calcium channel that contributes to T-type currents. Recently, two de novo missense variations, T797M and R1346H, of hCaV3.3 were identified in individuals with schizophrenia. Here we show that R1346H, but not T797M, is associated with lower hCaV3.3 protein levels, reduced glycosylation, and lower membrane surface levels of hCaV3.3 when expressed in human cell lines compared to wild-type...
October 19, 2016: Scientific Reports
Estelle Louiset, Céline Duparc, Sébastien Lenglet, Celso E Gomez-Sanchez, Hervé Lefebvre
In human adrenal, serotonin (5-HT), produced by mast cells located in zona glomerulosa, stimulates production of corticosteroids through a paracrine mechanism involving the 5-HT receptor type 4 (5-HT4). The aim of the present study was to investigate the transduction mechanisms associated with activation of 5-HT4 receptors in human adrenocortical cells. Our results show that 5-HT4 receptors are present in the outer adrenal cortex, both in glomerulosa and fasciculata zonae. In the zona glomerulosa. 5-HT4 receptor was detected both in immunopositive and immunonegative cells for 11β-hydroxylase, an enzyme involved in cortisol synthesis...
October 12, 2016: Molecular and Cellular Endocrinology
T Nguyen, S Johnston, L Clarke, P Smith, D Staines, S Marshall-Gradisnik
Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca(2+) ) cell signalling. Reduced TRPM3 has been identified in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca(2+) mobilisation has yet to be determined. Fifteen CFS/ME patients (mean age 48.82 ± 9.83 years) and 25 health controls (mean age 39.2 ± 12.12 years) were examined. Isolated NK cells were labelled with fluorescent antibodies to determine TRPM3, CD107a, and CD69 receptors on CD56(Dim) CD16(+) NK cells and CD56(Bright) CD16(Dim/-) NK cells...
October 11, 2016: Clinical and Experimental Immunology
O Maiques, A Macià, S Moreno, C Barceló, M Santacana, A Vea, J Herreros, S Gatius, E Ortega, J Valls, B J Chen, D Llobet-Navas, X Matias-Guiu, C Cantí, R M Marti
BACKGROUND AND OBJECTIVES: Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic nevi. We have recently reported that T-type Ca(2+) channels (TTCs) are upregulated in human melanoma and play an important role on cell proliferation. The aim of this study was to describe for the first time in formalin-fixed-paraffin-embedded tissue the immunoexpression of TT-Cs in biopsies of normal skin, acquired melanocytic nevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumor progression, their utility as prognostic markers and their possible use in targeted therapies...
October 8, 2016: British Journal of Dermatology
Tamanna Gandhi, Anu R Melge, C Gopi Mohan
Limited progress has been made in the quest to identify both selective and non-toxic T-type calcium channel blocking compounds. The present research work was directed toward slaking the same by identifying the selective three dimensional (3D) pharmacophore map for T-type calcium channel blockers (CCBs). Using HipHop module in the CATALYST 4.10 software, both selective and non-selective HipHop pharmacophore maps for T-type CCBs were developed to identify its important common pharmacophoric features. HipHop pharmacophore map of the selective T-type CCBs contained six different chemical features, namely ring aromatic (R), positive ionizable (P), two hydrophobic aromatic (Y), hydrophobic aliphatic (Z), hydrogen bond acceptor (H) and hydrogen bond donor (D)...
November 2016: Journal of Advanced Research
J Tamargo, Luis Miguel Ruilope
Voltage-gated Ca(2+) channels are the primary route of Ca(2+) entry in vascular smooth muscle cells, playing a key role in the regulation of arterial tone and blood pressure. Since the 60´s, L-type Ca(2+) channel blockers (CCBs) have been widely used for the treatment of hypertension. Areas covered. T-type Ca(2+) channels regulate vascular tone in small-resistance vessels and aldosterone secretion, and N-type channels expressed in sympathetic nerve terminals regulate the release of neurotransmitters. We performed a literature search in MEDLINE, PubMed and ClinicalTrials...
October 4, 2016: Expert Opinion on Investigational Drugs
Adam S Helms, Francisco J Alvarado, Jaime Yob, Vi T Tang, Francis Pagani, Mark W Russell, Héctor H Valdivia, Sharlene M Day
BACKGROUND: -Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS: -We analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8). RESULTS: -Gene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban (PLN), calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM compared to controls...
September 29, 2016: Circulation
Julieta Diaz-Juarez, Jorge Suarez, Federico Cividini, Brian T Scott, Tanja Diemer, Anzhi Dai, Wolfgang H Dillmann
Diabetic cardiomyopathy is associated with metabolic changes including decreased glucose oxidation (Gox) and increased fatty acid oxidation (FAox), which result in cardiac energetic deficiency. Diabetic hyperglycemia is a pathophysiological mechanism that triggers multiple maladaptive phenomena. The mitochondrial calcium uniporter (MCU) is the channel responsible for Ca(2+) uptake in mitochondria and free mitochondrial calcium concentration ([Ca(2+)]m) regulates mitochondrial metabolism. Experiments with cardiac myocytes (CM) exposed to simulated hyperglycemia revealed both reduced [Ca(2+)]m and MCU protein levels...
September 28, 2016: American Journal of Physiology. Cell Physiology
Joanna Lazniewska, Yuriy Rzhepetskyy, Fang-Xiong Zhang, Gerald W Zamponi, Norbert Weiss
T-type calcium channels are key contributors to neuronal physiology where they shape electrical activity of nerve cells and contribute to the release of neurotransmitters. Enhanced T-type channel expression has been causally linked to a number of pathological conditions including peripheral painful diabetic neuropathy. Recently, it was demonstrated that asparagine-linked glycosylation not only plays an essential role in regulating cell surface expression of Cav3.2 channels, but may also support glucose-dependent potentiation of T-type currents...
September 23, 2016: Pflügers Archiv: European Journal of Physiology
Tingting Wang, Ryan T Jones, Jenna M Whippen, Graeme W Davis
The homeostatic modulation of neurotransmitter release, termed presynaptic homeostatic potentiation (PHP), is a fundamental type of neuromodulation, conserved from Drosophila to humans, that stabilizes information transfer at synaptic connections throughout the nervous system. Here, we demonstrate that α2δ-3, an auxiliary subunit of the presynaptic calcium channel, is required for PHP. The α2δ gene family has been linked to chronic pain, epilepsy, autism, and the action of two psychiatric drugs: gabapentin and pregabalin...
September 13, 2016: Cell Reports
Alexandre Gironell, Juan Marin-Lahoz
BACKGROUND: T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated...
2016: Tremor and Other Hyperkinetic Movements
Y H Liu, Y P Wang, Y Wang, K T Ma, J Q Si, L Li
OBJECTIVE: The purpose of this paper was to study the electrophysiological properties and the type of potassium channels on cell membrane in the stria vascularis pericytes in cochlear of guinea pig. METHODS: Firstly examined the expression of the stria vascularis pericytes by desmin, a marker of pericytes, in cochlear of guinea pig with immunofluorescent method. Using whole-cell patch clamp recording techniques to observe electrophysiological properties in the cochlear pericytes in stria vascularis of guinea pig...
August 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Carolina Aguado, Sebastián García-Madrona, Mercedes Gil-Minguez, Rafael Luján
T-type calcium (Ca(2+)) channels play a central role in regulating membrane excitability in the brain. Although the contributions of T-type current to neuron output is often proposed to reflect a differential distribution of T-type channel subtypes to somato-dendritic compartments, their precise subcellular distributions in central neurons are not fully determined. Using histoblot and high-resolution immunoelectron microscopic techniques, we have investigated the expression, regional distribution and subcellular localization of T-type Cav3...
2016: Frontiers in Neuroanatomy
Adriana Galvan, Annaelle Devergnas, Damien Pittard, Gunasingh Masilamoni, Jocelyn Vuong, J Scott Daniels, Ryan D Morrison, Craig W Lindsley, Thomas Wichmann
Dopaminergic medications ameliorate many of the motor impairments of Parkinson's disease (PD). However, parkinsonism is often only partially reversed by these drugs, and they can have significant side effects. Therefore, a need remains for novel treatments of parkinsonism. Studies in rodents and preliminary clinical evidence have shown that T-type calcium channel (TTCC) antagonists have antiparkinsonian effects. However, most of the available studies utilized nonselective agents. We now evaluated whether systemic injections of the specific TTCC blocker ML218 have antiparkinsonian effects in MPTP-treated parkinsonian Rhesus monkeys...
September 20, 2016: ACS Chemical Neuroscience
Jung Hyun Kim, Ghilsoo Nam
A new series of aryls, including benzo[d]imidazole/isoxazole/pyrazole, conjugated to 3N-substituted-azabicyclo[3.1.0]hexane derivatives were designed and synthesized as inhibitors of T-type calcium channels. Among the synthesized compounds, 3N-R-substituted azabicyclo[3.1.0]hexane carboxamide derivatives containing 5-isobutyl-1-phenyl-pyrazole ring exhibited potent and selective T-channel inhibition and good metabolic stability without CYP450 inhibition. Compounds 10d and 10e contained hydrophobic substituents at the 3N-position and exhibited potent in vitro efficacy, as well as neuropathic pain alleviation in rats...
November 1, 2016: Bioorganic & Medicinal Chemistry
Ellie M Carrell, Aundrea R Coppola, Helen J McBride, Robert T Dirksen
Orai1 is a transmembrane protein that forms homomeric, calcium-selective channels activated by stromal interaction molecule 1 (STIM1) after depletion of intracellular calcium stores. In adult skeletal muscle, depletion of sarcoplasmic reticulum calcium activates STIM1/Orai1-dependent store-operated calcium entry. Here, we used constitutive and inducible muscle-specific Orai1 knockout (KO) mice to determine the acute and long-term developmental effects of Orai1 ablation on muscle structure and function. Skeletal muscles from constitutive, muscle-specific Orai1 KO mice exhibited normal postnatal growth and fiber type differentiation...
September 1, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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