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https://www.readbyqxmd.com/read/29129814/zinc-deficiency-promotes-cystitis-related-bladder-pain-by-enhancing-function-and-expression-of-cav3-2-in-mice
#1
Tomoka Ozaki, Junki Matsuoka, Maho Tsubota, Shiori Tomita, Fumiko Sekiguchi, Takeshi Minami, Atsufumi Kawabata
Cav3.2 T-type Ca(2+) channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Cav3.2, and enhanced by H2S that interacts with zinc. Cav3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Cav3.2 activity by H2S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Cav3...
November 9, 2017: Toxicology
https://www.readbyqxmd.com/read/29115500/roles-and-mechanisms-of-trpc3-and-the-plc%C3%AE-pkc-cpi-17-signaling-pathway-in-regulating-parturition
#2
Jing Chen, Dongming Zheng, Hong Cui, Sishi Liu, Lijuan Zhang, Caixia Liu
The aim of the current study was to investigate the role of phospholipase C (PLC)γ/protein kinase C (PKC)/C‑kinase‑activated protein phosphatase‑1 (CPI‑17) signaling pathways in uterine smooth muscle during parturition. Samples of uterine tissue were collected from pregnant patients who underwent a caesarean section for preterm delivery, full‑term delivery with labor onset, full‑term delivery without labor onset, and from a non‑pregnant control group undergoing surgery for cervical intraepithelial neoplasia III...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29082441/deletion-of-t-type-calcium-channels-cav3-1-or-cav3-2-attenuates-endothelial-dysfunction-in-aging-mice
#3
Anne D Thuesen, Kenneth Andersen, Kristina S Lyngsø, Mark Burton, Charlotte Brasch-Andersen, Paul M Vanhoutte, Pernille B L Hansen
Impairment of endothelial function with aging is accompanied by reduced nitric oxide (NO) production. T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis was that T-type channels contribute to the endothelial dysfunction of aging. Endothelial function was determined in mesenteric arteries (perfusion) and aortae (isometric contraction) of young and old wild-type (WT), Cav3.1, and Cav3.2 knockout mice. NO production was measured by fluorescence imaging in mesenteric arteries...
October 29, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29074257/discovery-and-evaluation-of-cav3-2-selective-t-type-calcium-channel-blockers
#4
Olivier Bezençon, Luboš Remeň, Sylvia Richard, Catherine Roch, Melanie Kessler, Eric A Ertel, Richard Moon, Jacques Mawet, Thomas Pfeifer, Bruno Capeleto
We identified and characterized a series of pyrrole amides as potent, selective Cav3.2-blockers. This series culminated with the identification of pyrrole amides 13b and 26d, with excellent potencies and/or selectivities toward the Cav3.1- and Cav3.3-channels. These compounds display poor physicochemical and DMPK properties, making their use difficult for in vivo applications. Nevertheless, they are well-suited for in vitro studies.
September 30, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29073181/modulation-of-t-type-ca2-channels-by-lavender-and-rosemary-extracts
#5
Chaymae El Alaoui, Jean Chemin, Taoufiq Fechtali, Philippe Lory
Medicinal plants represent a significant reservoir of unexplored substances for early-stage drug discovery. Of interest, two flowering Mediterranean plants have been used for thousands of years for their beneficial effects on nervous disorders, including anxiety and mood. However, the therapeutic potential of these plants regarding their ability to target ion channels and neuronal excitability remains largely unknown. Towards this goal, we have investigated the ability of Lavender and Rosemary to modulate T-type calcium channels (TTCCs)...
2017: PloS One
https://www.readbyqxmd.com/read/29066309/discovery-and-evaluation-of-cav3-1-selective-t-type-calcium-channel-blockers
#6
Olivier Bezençon, Luboš Remeň, Sylvia Richard, Catherine Roch, Melanie Kessler, Richard Moon, Jacques Mawet, Eric A Ertel, Thomas Pfeifer, Bruno Capeleto
We identified and characterized a series of pyrazole amides as potent, selective Cav3.1-blockers. This series culminated with the identification of pyrazole amides 5a and 12d, with excellent potencies and/or selectivities toward the Cav3.2- and Cav3.3-channels. This compound displays poor DMPK properties, making its use difficult for in vivo applications. Nevertheless, this compound as well as analogous ones are well-suited for in vitro studies.
October 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29052595/corrigendum-hydrogen-sulfide-induced-itch-requires-activation-of-cav3-2-t-type-calcium-channel-in-mice
#7
Xue-Long Wang, Bin Tian, Ya Huang, Xiao-Yan Peng, Li-Hua Chen, Jun-Cheng Li, Tong Liu
This corrects the article DOI: 10.1038/srep16768.
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29036189/inhibition-of-cug-binding-protein-1-and-activation-of-caspases-are-critically-involved-in-piperazine-derivative-bk10007s-induced-apoptosis-in-hepatocellular-carcinoma-cells
#8
Ju-Ha Kim, Hee Young Kwon, Dong Hoon Ryu, Min-Ho Nam, Bum Sang Shim, Jin Han Kim, Jae Yeol Lee, Sung-Hoon Kim
Though piperazine derivative BK10007S was known to induce apoptosis in pancreatic cancer xenograft model as a T-type CaV3.1 a1G isoform calcium channel blocker, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the antitumor mechanism of BK10007S was elucidated in hepatocellular carcinoma cells (HCCs). Herein, BK10007S showed significant cytotoxicity by 3-[4,5-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) assay and anti-proliferative effects by colony formation assay in HepG2 and SK-Hep1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/29027927/conotoxins-as-tools-to-understand-the-physiological-function-of-voltage-gated-calcium-cav-channels
#9
REVIEW
David Ramírez, Wendy Gonzalez, Rafael A Fissore, Ingrid Carvacho
Voltage-gated calcium (CaV) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV1.1-1.4; CaV2.1-2.3) and Low-voltage activated (LVA, CaV3.1-3.3)...
October 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29016703/%C3%AE-arrestin-2-mediates-cardiac-ischemia-reperfusion-injury-via-inhibiting-gpcr-independent-cell-survival-signalling
#10
Yimei Wang, Li Jin, Ying Song, Mao Zhang, Dan Shan, Yuli Liu, Meng Fang, Fengxiang Lv, Rui-Ping Xiao, Yan Zhang
Aims: Ischemic heart disease is a leading cause of morbidity and mortality worldwide. Although timely restoration of coronary blood flow (reperfusion) is the most effective therapeutics of myocardial infarction, reperfusion causes further cardiac damage, i.e. ischemia-reperfusion (I/R) injury. β-arrestins (Arrbs) have been traditionally defined as negative regulators of G protein-coupled receptor (GPCR) signalling, but recent studies have shown that they are essential for G protein-independent, GPCR-mediated biased signalling...
November 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28981925/-clinical-and-genetic-study-of-a-chinese-family-affected-with-caveolinopathies
#11
Hongbing Nie, Xiangbin Wu, Jinju Lyu, Jing Zhu, Dandan Tan
OBJECTIVE: To analyze clinical features and genetic mutations in a Chinese family affected with autosomal dominant caveolinopathies. METHODS: Clinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples with a standard procedure. Next generation sequencing was carried out for the proband, and direct sequencing was employed to detect potential mutation of the CAV gene. RESULTS: The proband presented with slowly progressing distal muscle weakness and atrophy, especially distal upper limbs and muscular soreness during early childhood, with her CK level moderately elevated and EMG showing myogenic and neurogenic injuries...
October 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28974495/prenatal-hypoxia-induced-dysfunction-in-cerebral-arteries-of-offspring-rats
#12
Jiaqi Tang, Na Li, Xueyi Chen, Qinqin Gao, Xiuwen Zhou, Yingying Zhang, Bailin Liu, Miao Sun, Zhice Xu
BACKGROUND: Hypoxia during pregnancy could cause abnormal development and lead to increased risks of vascular diseases in adults. This study determined angiotensin II (AII)-mediated vascular dysfunction in offspring middle cerebral arteries (MCA). METHODS AND RESULTS: Pregnant rats were subjected to hypoxia. Vascular tension in offspring MCA by AII with or without inhibitors, calcium channel activities, and endoplasmic reticulum calcium stores were tested. Whole-cell patch clamping was used to investigate voltage-dependent calcium channel currents...
October 3, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28974111/in-vitro-neurotoxicity-by-ropivacaine-is-reduced-by-silencing-cav3-3-t-type-calcium-subunits-in-neonatal-rat-sensory-neurons
#13
Xianjie Wen, Hua Liang, Heng Li, Weiming Ou, Han-Bing Wang, Hongzhen Liu, Shijie Li
Neurotoxicity of local anaesthetics has been alerted by more and more peoples. Cav3.1 and Cav3.2 T-type calcium channels were closely related with local anaesthetics toxicity. However, the role of Cav3.3, another subtype of the T-type calcium channel, on the neurotoxicity induced by local anaesthetics remains unclear. CaMKIIγ is a kind of multifunctional kinase and associated with a variety of physiological and pathological process. T-type calcium channel is closely related with CaMKIIγ. Up-regulation CaMKIIγ can increase T-type currents at the dorsal root ganglia (DRG)...
October 3, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28972185/calmodulin-regulates-cav3-t-type-channels-at-their-gating-brake
#14
Jean Chemin, Valentina Taiakina, Arnaud Monteil, Michael Piazza, Wendy Guan, Robert F Stephens, Ashraf Kitmitto, Zhiping P Pang, Annette C Dolphin, Edward Perez-Reyes, Thorsten Dieckmann, Joseph Guy Guillemette, J David Spafford
Calcium (Cav1 and Cav2) and sodium channels possess homologous CaM-binding motifs, known as IQ motifs in their C-termini, which associate with calmodulin (CaM), a universal calcium sensor. Cav3 T-type channels, which serve as pacemakers of the mammalian brain and heart, lack a C-terminal IQ motif. We illustrate that T-type channels associate with CaM using co-immunoprecipitation experiments and single particle cryo-electron microscopy. We demonstrate that protostome invertebrate (LCav3) and human Cav3.1, Cav3...
September 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28933792/a-common-haplotype-containing-functional-cacna1h-variants-is-frequently-coinherited-with-increased-tpsab1-copy-number
#15
Jonathan J Lyons, Stephanie C Stotz, Jack Chovanec, Yihui Liu, Katie L Lewis, Celeste Nelson, Thomas DiMaggio, Nina Jones, Kelly D Stone, Heejong Sung, Leslie G Biesecker, Michael A Colicos, Joshua D Milner
PurposeCaV3.2 signaling contributes to nociception, pruritus, gastrointestinal motility, anxiety, and blood pressure homeostasis. This calcium channel, encoded by CACNA1H, overlaps the human tryptase locus, wherein increased TPSAB1 copy number causes hereditary α-tryptasemia. Germ-line CACNA1H variants may contribute to the variable expressivity observed with this genetic trait.MethodsTryptase-encoding sequences at TPSAB1 and TPSB2, and TPSG1 and CACNA1H variants were genotyped in 46 families with hereditary α-tryptasemia syndrome...
September 21, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28916724/a-novel-mechanism-for-ca-2-calmodulin-dependent-protein-kinase-ii-targeting-to-l-type-ca-2-channels-that-initiates-long-range-signaling-to-the-nucleus
#16
Xiaohan Wang, Christian R Marks, Tyler L Perfitt, Terunaga Nakagawa, Amy Lee, David A Jacobson, Roger J Colbran
Neuronal excitation can induce new mRNA transcription, a phenomenon called excitation-transcription (E-T) coupling. Among several pathways implicated in E-T coupling, activation of voltage-gated L-type Ca(2+) channels (LTCCs) in the plasma membrane can initiate a signaling pathway that ultimately increases nuclear CREB phosphorylation and, in most cases, expression of immediate early genes. Initiation of this long-range pathway has been shown to require recruitment of Ca(2+)-sensitive enzymes to a nanodomain in the immediate vicinity of the LTCC by an unknown mechanism...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28912545/the-cacna1h-mutation-in-the-gaers-model-of-absence-epilepsy-enhances-t-type-ca-2-currents-by-altering-calnexin-dependent-trafficking-of-cav3-2-channels
#17
Juliane Proft, Yuriy Rzhepetskyy, Joanna Lazniewska, Fang-Xiong Zhang, Stuart M Cain, Terrance P Snutch, Gerald W Zamponi, Norbert Weiss
Low-voltage-activated T-type calcium channels are essential contributors to the functioning of thalamocortical neurons by supporting burst-firing mode of action potentials. Enhanced T-type calcium conductance has been reported in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and proposed to be causally related to the overall development of absence seizure activity. Here, we show that calnexin, an endoplasmic reticulum integral membrane protein, interacts with the III-IV linker region of the Cav3...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899000/rhoa-rock-signalling-is-necessary-for-lateralization-and-differentiation-of-the-developing-sinoatrial-node
#18
Rebecca Vicente-Steijn, Tim P Kelder, Leon G Tertoolen, Lambertus J Wisse, Daniël A Pijnappels, Robert E Poelmann, Martin J Schalij, Marco C deRuiter, Adriana C Gittenberger-de Groot, Monique R M Jongbloed
Aims: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28880874/discovery-and-mode-of-action-of-a-novel-analgesic-%C3%AE-toxin-from-the-african-spider-ceratogyrus-darlingi
#19
Silmara R Sousa, Joshua S Wingerd, Andreas Brust, Christopher Bladen, Lotten Ragnarsson, Volker Herzig, Jennifer R Deuis, Sebastien Dutertre, Irina Vetter, Gerald W Zamponi, Glenn F King, Paul F Alewood, Richard J Lewis
Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider Ceratogyrus darlingi. Cd1a reversibly paralysed sheep blowflies (PD50 of 1318 pmol/g) and inhibited human Cav2.2 (IC50 2.6 μM) but not Cav1.3 or Cav3.1 (IC50 > 30 μM) in fluorimetric assays...
2017: PloS One
https://www.readbyqxmd.com/read/28837624/rare-variants-in-genes-encoding-the-cardiac-sodium-channel-and-associated-compounds-and-their-impact-on-outcome-of-catheter-ablation-of-atrial-fibrillation
#20
Daniela Husser, Laura Ueberham, Gerhard Hindricks, Petra Büttner, Christie Ingram, Peter Weeke, M Benjamin Shoemaker, Volker Adams, Arash Arya, Philipp Sommer, Dawood Darbar, Dan M Roden, Andreas Bollmann
AIM: Rare variants of genes encoding the cardiac sodium channel and associated compounds have been linked with atrial fibrillation (AF). Nevertheless, current expert consensus does not support genetic testing in AF, which is in part based on the fact that "there is no therapeutic impact derived from AF genetic test results". However, there are no studies available supporting this recommendation. Consequently, this study analyzed the impact of rare variants affecting the cardiac sodium channel on rhythm outcome of AF catheter ablation...
2017: PloS One
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