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https://www.readbyqxmd.com/read/28253495/tacrolimus-triggers-transient-receptor-potential-vanilloid-1-dependent-relapse-of-pancreatitis-related-pain-in-mice
#1
Yuka Terada, Maho Tsubota, Hiiragi Sugo, Kohei Wakitani, Fumiko Sekiguchi, Kyoichi Wada, Mitsutaka Takada, Akira Oita, Atsufumi Kawabata
Transient receptor potential vanilloid-1 (TRPV1) expressed in nociceptors is directly phosphorylated and activated by protein kinase C, and involved in the signaling of pancreatic pain. On the other hand, Cav3.2 T-type Ca2+ channels expressed in nociceptors are functionally upregulated by phosphorylation with protein kinase A and also play a role in pancreatitis-related pain. Calcineurin, a phosphatase, negatively regulates various channel functions including TRPV1, and calcineurin inhibitor-induced pain syndrome by tacrolimus, a calcineurin inhibitor, used as an immunosuppressant, has been a clinical problem...
March 3, 2017: Pharmacology
https://www.readbyqxmd.com/read/28145504/honeybee-locomotion-is-impaired-by-am-cav3-low-voltage-activated-ca-2-channel-antagonist
#2
M Rousset, C Collet, T Cens, F Bastin, V Raymond, I Massou, C Menard, J-B Thibaud, M Charreton, M Vignes, M Chahine, J C Sandoz, P Charnet
Voltage-gated Ca(2+) channels are key transducers of cellular excitability and participate in several crucial physiological responses. In vertebrates, 10 Ca(2+) channel genes, grouped in 3 families (CaV1, CaV2 and CaV3), have been described and characterized. Insects possess only one member of each family. These genes have been isolated in a limited number of species and very few have been characterized although, in addition to their crucial role, they may represent a collateral target for neurotoxic insecticides...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28122853/caveolin-2-a-facultative-marker-of-unfavourable-prognosis-in-long-term-patency-rate-of-internal-thoracic-artery-grafts-used-in-coronary-artery-bypass-grafting-preliminary-report
#3
Agnieszka Malinska, Zuzanna Podemska, Patrycja Sujka-Kordowska, Wojciech Witkiewicz, Michal Nowicki, Bartlomiej Perek, Martin Witt
OBJECTIVES: Intimal hyperplasia leading to graft failure in patients undergoing coronary artery bypass grafting (CABG) is related to vascular smooth muscle cells (SMCs) proliferation. SMCs respond to a variety of mediators, the most important of which is platelet-derived growth factor (PDGF). The platelet-derived growth factor-induced cellular response has been shown to be mediated by caveolins. The aim of this study was to analyze CAV1-3 expression in internal thoracic artery (ITA) grafts used in CABG and correlate their expression with graft occlusion...
January 25, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28093211/pharmacological-properties-of-sak3-a-novel-t-type-voltage-gated-ca-2-channel-enhancer
#4
Yasushi Yabuki, Kazuya Matsuo, Hisanao Izumi, Hidaka Haga, Takashi Yoshida, Minoru Wakamori, Akikazu Kakei, Kenji Sakimura, Takaichi Fukuda, Kohji Fukunaga
T-type voltage-gated Ca(2+) channels (T-VGCCs) function in the pathophysiology of epilepsy, pain and sleep. However, their role in cognitive function remains unclear. We previously reported that the cognitive enhancer ST101, which stimulates T-VGCCs in rat cortical slices, was a potential Alzheimer's disease therapeutic. Here, we introduce a more potent T-VGCC enhancer, SAK3 (ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo [1,2-a]pyridin]-2-ene-3-carboxylate), and characterize its pharmacological properties in brain...
January 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28055302/t-type-ca-2-channels-and-autoregulation-of-local-blood-flow
#5
Lars Jørn Jensen, Morten Schak Nielsen, Max Salomonsson, Charlotte Mehlin Sørensen
L-type voltage gated Ca(2+) channels are considered to be the primary source of calcium influx during the myogenic response. However, many vascular beds also express T-type voltage gated Ca(2+) channels. Recent studies suggest that these channels may also play a role in autoregulation. At low pressures (40-80 mmHg) T-type channels affect myogenic responses in cerebral and mesenteric vascular beds. T-type channels also seem to be involved in skeletal muscle autoregulation. This review discusses the expression and role of T-type voltage gated Ca(2+) channels in the autoregulation of several different vascular beds...
January 5, 2017: Channels
https://www.readbyqxmd.com/read/28054154/interstitial-cell-modulation-of-pyeloureteric-peristalsis-in-the-mouse-renal-pelvis-examined-using-fibsem-tomography-and-calcium-indicators
#6
Hikaru Hashitani, Michael J Nguyen, Haruka Noda, Retsu Mitsui, Ryuhei Higashi, Keisuke Ohta, Kei-Ichiro Nakamura, Richard J Lang
Typical and atypical smooth muscle cells (TSMCs and ASMCs, respectively) and interstitial cells (ICs) within the pacemaker region of the mouse renal pelvis were examined using focused ion beam scanning electron (FIB SEM) tomography, immunohistochemistry and Ca(2+) imaging. Individual cells within 500-900 electron micrograph stacks were volume rendered and associations with their neighbours established. 'Ribbon-shaped', Ano1 Cl(-) channel immuno-reactive ICs were present in the adventitia and the sub-urothelial space adjacent to the TSMC layer...
January 4, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28039202/caveolae-specific-activation-loop-between-camkii-and-l-type-ca2-channel-aggravates-cardiac-hypertrophy-in-%C3%AE-1-adrenergic-stimulation
#7
Kota Tonegawa, Wataru Otsuka, Shohei Kumagai, Sachi Matsunami, Nao Hayamizu, Shota Tanaka, Kazumasa Moriwaki, Masanori Obana, Makiko Maeda, Michio Asahi, Hiroshi Kiyonari, Yasushi Fujio, Hiroyuki Nakayama
AIMS: Activation of CaMKII induces a myriad of biological processes and plays dominant roles in cardiac hypertrophy. Caveolar microdomain contains many CaMKII targets, including L-type Ca2+ channel (LTCC) complex, and serves as a signalling platform. The location of CaMKII activation is thought to be critical, however, the roles of CaMKII in caveolae are still elusive due to lack of methodology for the assessment of caveolae-specific activation. Our aim was to develop a novel tool for the specific analysis of CaMKII activation in caveolae, and to determine the functional role of caveolar CaMKII in cardiac hypertrophy...
December 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28007571/multiple-nickel-sensitive-targets-elicit-cardiac-arrhythmia-in-isolated-mouse-hearts-after-pituitary-adenylate-cyclase-activating-polypeptide-mediated-chronotropy
#8
Etienne E Tevoufouet, Erastus N Nembo, Fabian Distler, Felix Neumaier, Jürgen Hescheler, Filomain Nguemo, Toni Schneider
The pituitary adenylate cyclase-activating polypeptide (PACAP)-27 modulates various biological processes, from the cellular level to function specification. However, the cardiac actions of this neuropeptide are still under intense studies. Using control (+|+) and mice lacking (-|-) either R-type (Cav2.3) or T-type (Cav3.2) Ca(2+) channels, we investigated the effects of PACAP-27 on cardiac activity of spontaneously beating isolated perfused hearts. Superfusion of PACAP-27 (20nM) caused a significant increase of baseline heart frequency in Cav2...
December 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27974205/trpv1-nociceptor-activity-initiates-usp5-t-type-channel-mediated-plasticity
#9
Patrick Stemkowski, Agustin García-Caballero, Vinicius De Maria Gadotti, Said M'Dahoma, Shuo Huang, Stefanie Alice Gertrud Black, Lina Chen, Ivana Assis Souza, Zizhen Zhang, Gerald Werner Zamponi
Peripheral nerve injury and tissue inflammation result in upregulation of the deubiquitinase USP5, thus causing a dysregulation of T-type calcium channel activity and increased pain sensitivity. Here, we have explored the role of afferent fiber activity in this process. Conditioning stimulation of optogenetically targeted cutaneous TRPV1 expressing nociceptors, but not that of non-nociceptive fibers, resulted in enhanced expression of USP5 in mouse dorsal root ganglia and spinal dorsal horn, along with decreased withdrawal thresholds for thermal and mechanical stimuli that abated after 24 hr...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27931022/hydrogen-sulfide-and-t-type-ca2-channels-in-pain-processing-neuronal-differentiation-and-neuroendocrine-secretion
#10
REVIEW
Kazuki Fukami, Kazuki Fukami, Fumiko Sekiguchi, Fumiko Sekiguchi, Atsufumi Kawabata, Atsufumi Kawabata
BACKGROUND: Hydrogen sulfide (H2S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H2S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Cav3.2 T-type Ca2+ channels mediate some of the biological activity of H2S, we focus on the role of the H2S/Cav3...
2017: Pharmacology
https://www.readbyqxmd.com/read/27919294/heantos-4-a-natural-plant-extract-used-in-the-treatment-of-drug-addiction-modulates-t-type-calcium-channels-and-thalamocortical-burst-firing
#11
Stuart M Cain, Soyon Ahn, Esperanza Garcia, Yiming Zhang, Zeina Waheed, John R Tyson, Yi Yang, Tran Van Sung, Anthony G Phillips, Terrance P Snutch
Heantos-4 is a refined combination of plant extracts currently approved to treat opiate addiction in Vietnam. In addition to its beneficial effects on withdrawal and prevention of relapse, reports of sedation during clinical treatment suggest that arousal networks in the brain may be recruited during Heantos administration. T-type calcium channels are implicated in the generation of sleep rhythms and in this study we examined whether a Heantos-4 extraction modulates T-type calcium channel currents generated by the Cav3...
December 5, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27913207/overexpression-of-stim1-in-neurons-in-mouse-brain-improves-contextual-learning-and-impairs-long-term-depression
#12
Łukasz Majewski, Filip Maciąg, Paweł M Boguszewski, Iga Wasilewska, Grzegorz Wiera, Tomasz Wójtowicz, Jerzy Mozrzymas, Jacek Kuznicki
STIM1 is an endoplasmic reticulum calcium sensor that is involved in several processes in neurons, including store-operated calcium entry. STIM1 also inhibits voltage-gated calcium channels, such as Cav1.2 and Cav3.1, and is thus considered a multifunctional protein. The aim of this work was to investigate the ways in which transgenic neuronal overexpression of STIM1 in FVB/NJ mice affects animal behavior and the electrophysiological properties of neurons in acute hippocampal slices. We overexpressed STIM1 from the Thy1...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#13
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27902567/dorsal-root-ganglion-neurons-become-hyperexcitable-and-increase-expression-of-voltage-gated-t-type-calcium-channels-cav3-2-in-paclitaxel-induced-peripheral-neuropathy
#14
Yan Li, Claudio Esteves Tatsui, Laurence D Rhines, Robert Y North, Daniel S Harrison, Ryan M Cassidy, Caj A Johansson, Alyssa K Kosturakis, Denaya D Edwards, Hongmei Zhang, Patrick M Dougherty
Here, it is shown that paclitaxel-induced neuropathy is associated with the development of spontaneous activity (SA) and hyperexcitability in dorsal root ganglion (DRG) neurons that is paralleled by increased expression of low-voltage-activated calcium channels (T-type; Cav3.2). The percentage of DRG neurons showing SA and the overall mean rate of SA were significantly higher at day 7 in rats receiving paclitaxel treatment than in rats receiving vehicle. Cav3.2 expression was increased in L4-L6 DRG and spinal cord segments in paclitaxel-treated rats, localized to small calcitonin gene-related peptide and isolectin B4 expressing DRG neurons and to glial fibrillary acidic protein-positive spinal cord cells...
March 2017: Pain
https://www.readbyqxmd.com/read/27882143/expression-of-connexin-43-ion-channels-and-ca-2-handling-proteins-in-rat-pulmonary-vein-cardiomyocytes
#15
Yaqiong Xiao, Xue Cai, Andrew Atkinson, Sunil Jit Logantha, Mark Boyett, Halina Dobrzynski
Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to be triggered by ectopic beats, originating primarily in the myocardial sleeves surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac arrhythmias remain unclear. To investigate this, frozen sections of heart and lung tissue from adult rats without arrhythmia were obtained in different planes, stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43), caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), Nav1...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27843503/review-cav2-3-r-type-voltage-gated-ca-2-channels-functional-implications-in-convulsive-and-non-convulsive-seizure-activity
#16
Carola Wormuth, Andreas Lundt, Christina Henseler, Ralf Müller, Karl Broich, Anna Papazoglou, Marco Weiergräber
BACKGROUND: Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca(2+) channels are of central relevance in these processes. In particular, they are key elements in the etiopathogenesis of numerous seizure types and epilepsies. Earlier studies predominantly targeted on Cav2.1 P/Q-type and Cav3.2 T-type Ca(2+) channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Cav2...
2016: Open Neurology Journal
https://www.readbyqxmd.com/read/27772553/cav3-mutation-in-a-patient-with-transient-hyperckemia-and-myalgia
#17
Anna Macias, Tomasz Gambin, Przemyslaw Szafranski, Shalini N Jhangiani, Anna Kolasa, Ewa Obersztyn, James R Lupski, Pawel Stankiewicz, Anna Kaminska
Mutations in caveolin-3 (CAV3) can lead to different clinical phenotypes affecting skeletal or cardiac muscles. Here, we describe a patient with Klinefelter syndrome, ulcerative colitis and Sjögren syndrome, who developed transient hyperCKemia, myalgia and mild muscular weakness. Using whole exome sequencing (WES), a missense mutation G169A was found in the CAV3 gene. In addition, we identified a homozygous frameshift deletion in MS4A12 that may contribute to inflammatory bowel disease, further demonstrating usefulness of WES in dual molecular diagnoses...
November 2016: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/27765616/chronic-intrathecal-infusion-of-t-type-calcium-channel-blockers-attenuates-cav3-2-upregulation-in-nerve-ligated-rats
#18
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...
September 2016: Acta Anaesthesiologica Taiwanica: Official Journal of the Taiwan Society of Anesthesiologists
https://www.readbyqxmd.com/read/27756899/a-rare-schizophrenia-risk-variant-of-cacna1i-disrupts-cav3-3-channel-activity
#19
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
https://www.readbyqxmd.com/read/27742704/na-k-cl-cotransporter-nkcc-maintains-the-chloride-gradient-to-sustain-pacemaker-activity-in-interstitial-cells-of-cajal
#20
Mei Hong Zhu, Tae Sik Sung, Masaaki Kurahashi, Lauren E O'Kane, Kate O'Driscoll, Sang Don Koh, Kenton M Sanders
Interstitial cells of Cajal (ICC) generate electrical slow waves by coordinated openings of ANO1 channels, a Ca(2+)-activated Cl(-) (CaCC) conductance. Efflux of Cl(-) during slow waves must be significant, as there is high current density during slow-wave currents and slow waves are of sufficient magnitude to depolarize the syncytium of smooth muscle cells and PDGFRα(+) cells to which they are electrically coupled. We investigated how the driving force for Cl(-) current is maintained in ICC. We found robust expression of Slc12a2 (which encodes an Na(+)-K(+)-Cl(-) cotransporter, NKCC1) and immunohistochemical confirmation that NKCC1 is expressed in ICC...
December 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
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