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T-type calcium channel

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https://www.readbyqxmd.com/read/27904663/t-type-calcium-channel-blocker-attenuates-unilateral-ureteral-obstruction-induced-renal-interstitial-fibrosis-by-activating-the-nrf2-antioxidant-pathway
#1
Sungjin Chung, Soojeong Kim, Minyoung Kim, Eun Sil Koh, Hye Eun Yoon, Ho-Shik Kim, Cheol Whee Park, Yoon Sik Chang, Seok Joon Shin
Besides its effect on high blood pressure, T-type calcium channel blocker is renoprotective in experimental models of renal fibrosis. However, the exact mechanism of T-type calcium channel blocker on tubulointerstitial fibrosis is unclear. We investigated whether the renoprotective effect of T-type calcium channel blocker is associated with modulation of the signaling of oxidative stress-induced renal fibrosis. Treatment with a non-hypotensive dose of efonidipine, a T-type calcium channel blocker, or nifedipine, an L-type channel blocker, was initiated one day before unilateral ureteral obstruction (UUO) in C57BL6/J mice, and was continued until 3 and 7 days after UUO...
2016: American Journal of Translational Research
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
#2
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 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 of paclitaxel treatment than in rats receiving vehicle. Cav3.2 expression was increased in L4-6 DRG and spinal cord segments in paclitaxel-treated rats, localized to small calcitonin gene-related peptide expressing and isolectin B4 expressing DRG neurons and to glial fibrillary acidic protein-positive spinal cord cells...
November 24, 2016: Pain
https://www.readbyqxmd.com/read/27893045/association-of-3-different-antihypertensive-medications-with-hip-and-pelvic-fracture-risk-in-older-adults-secondary-analysis-of-a-randomized-clinical-trial
#3
Rachel Puttnam, Barry R Davis, Sara L Pressel, Paul K Whelton, William C Cushman, Gail T Louis, Karen L Margolis, Suzanne Oparil, Jeffrey Williamson, Alokananda Ghosh, Paula T Einhorn, Joshua I Barzilay
Importance: On the basis of observational studies, the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Data from randomized clinical trials are lacking. Objective: To examine whether the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Design, Setting, and Participants: Using Veterans Affairs and Medicare claims data, this study examined hip and pelvic fracture hospitalizations in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an angiotensin-converting enzyme inhibitor (lisinopril)...
November 21, 2016: JAMA Internal Medicine
https://www.readbyqxmd.com/read/27888388/cardiac-bin1-cbin1-is-a-regulator-of-cardiac-contractile-function-and-an-emerging-biomarker-of-heart-muscle-health
#4
REVIEW
Kang Zhou, Tingting Hong
In recent decades, a cardiomyocyte membrane scaffolding protein bridging integrator 1 (BIN1) has emerged as a critical multifunctional regulator of transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes. Encoded by a single gene with 20 exons that are alternatively spliced, more than ten BIN1 protein isoforms are expressed with tissue and disease specificity. The recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or BIN1+13+17) plays a crucial role in organizing membrane microfolds within cardiac t-tubules...
November 23, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27823926/cisplatin-induced-neuropathic-pain-is-mediated-by-upregulation-of-n-type-voltage-gated-calcium-channels-in-dorsal-root-ganglion-neurons
#5
Markus Leo, Linda-Isabell Schmitt, Martin Erkel, Margarita Melnikova, Jürgen Thomale, Tim Hagenacker
Cisplatin is important in the treatment of various types of cancer. Although it is highly effective, it also has severe side effects, with neurotoxicity in dorsal root ganglion (DRG) neurons being one of the most common. The key mechanisms of neurotoxicity are still controversially discussed; however, disturbances of the calcium homeostasis in DRG neurons have been suggested to mediate cisplatin neurotoxicity. By using the whole-cell patch-clamp technique, immunostaining and behavioral experiments with Sprague-Dawley rats, we examined the influence of short- and long-term exposure to cisplatin on voltage-gated calcium channel (VGCC) currents (ICa(V)) in small DRG neurons...
November 5, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27798140/conditional-deletion-of-the-l-type-calcium-channel-cav1-2-in-oligodendrocyte-progenitor-cells-affects-postnatal-myelination-in-mice
#6
Veronica T Cheli, Diara A Santiago González, Tenzing Namgyal Lama, Vilma Spreuer, Vance Handley, Geoffrey G Murphy, Pablo M Paez
: To determine whether L-type voltage-operated Ca(2+) channels (L-VOCCs) are required for oligodendrocyte progenitor cell (OPC) development, we generated an inducible conditional knock-out mouse in which the L-VOCC isoform Cav1.2 was postnatally deleted in NG2-positive OPCs. A significant hypomyelination was found in the brains of the Cav1.2 conditional knock-out (Cav1.2(KO)) mice specifically when the Cav1.2 deletion was induced in OPCs during the first 2 postnatal weeks. A decrease in myelin proteins expression was visible in several brain structures, including the corpus callosum, cortex, and striatum, and the corpus callosum of Cav1...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27793923/enhancing-the-therapeutic-efficacy-of-2-deoxyglucose-in-breast-cancer-cells-using-cell-cycle-synchronization
#7
Su Jin Lee, Bok-Nam Park, Jung Hyun Roh, Young-Sil An, Hoon Hur, Joon-Kee Yoon
AIM: We assessed the effect of cell-cycle synchronization using the T-type calcium channel inhibitor mibefradil on the anticancer effects of 2-deoxy-D-glucose (2-DG) and glucose metabolism in breast cancer cells. MATERIALS AND METHODS: MDA-MB-231 cells were treated with mibefradil, followed by 2-DG with/without paclitaxel, then cells were assessed for viability. Glucose metabolism was evaluated by (3)H-2-DG uptake, lactate concentration, and membrane glucose transporter 1 expression after mibefradil treatment...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27785644/effect-of-ica-l-blockade-on-adrenergic-stimulation-in-developing-heart
#8
T L Zefirov, A M Kuptsova, R G Biktemirova, N I Ziyatdinova, A L Zefirov
The effect of verapamil-induced blockade of L-type calcium ionic currents (ICa,L) on the action of non-selective adrenergic cardiac stimulation by norepinephrine was examined during different periods of early postnatal ontogeny. In 1-week-old rats, intravenous norepinephrine induced a short-term tachycardia both with and without preliminary injected verapamil. In 3-week-old rats, norepinephrine alone produced no chronotropic effect; in contrast, it induced a biphasic tachycardia in verapamil-treated rats. In 6- and 20-month-old rats, norepinephrine induced a short-term tachycardia, which could be prevented by verapamil...
October 26, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27782747/three-types-of-ion-channels-in-the-cell-membrane-of-mouse-fibroblasts
#9
M Koselski, A Olszewska, A Hordyjewska, T Małecka-Massalska, K Trebacz
Patch clamp recordings carried out in the inside-out configuration revealed activity of three kinds of channels: nonselective cation channels, small-conductance K(+) channels, and large-conductance anion channels. The nonselective cation channels did not distinguish between Na(+) and K(+). The unitary conductance of these channels reached 28 pS in a symmetrical concentration of 200 mM NaCl. A lower value of this parameter was recorded for the small-conductance K(+) channels and in a 50-fold gradient of K(+) (200 mM/4 mM) it reached 8 pS...
October 26, 2016: Physiological Research
https://www.readbyqxmd.com/read/27781369/ion-channels-ion-channel-receptors-and-visceral-hypersensitivity-in-irritable-bowel-syndrome
#10
REVIEW
I M Fuentes, J A Christianson
Ion channels are expressed throughout the gastrointestinal system and regulate nearly every aspect of digestion, including fluid secretion and absorption, motility, and visceral sensitivity. It is therefore not surprising that in the setting of functional bowel disorders, such as irritable bowel syndrome (IBS), ion channels are often altered in terms of expression level and function and are a target of pharmacological intervention. This is particularly true of their role in driving abdominal pain through visceral hypersensitivity (VH), which is the main reason IBS patients seek medical care...
November 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27765616/chronic-intrathecal-infusion-of-t-type-calcium-channel-blockers-attenuates-cav3-2-upregulation-in-nerve-ligated-rats
#11
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
https://www.readbyqxmd.com/read/27763639/functional-kca1-1-channels-are-crucial-for-regulating-the-proliferation-migration-and-differentiation-of-human-primary-skeletal-myoblasts
#12
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
https://www.readbyqxmd.com/read/27763328/it-takes-two-t-to-shape-immunity-emerging-role-for-t-type-calcium-channels-in-immune-cells
#13
Lubica Lacinova, Norbert Weiss
No abstract text is available yet for this article.
October 2016: General Physiology and Biophysics
https://www.readbyqxmd.com/read/27759880/ph%C3%AE-1%C3%AE-acts-as-a-trpa1-antagonist-with-antinociceptive-effects-in-mice
#14
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
https://www.readbyqxmd.com/read/27756899/a-rare-schizophrenia-risk-variant-of-cacna1i-disrupts-cav3-3-channel-activity
#15
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/27743992/role-of-camp-pka-pathway-and-t-type-calcium-channels-in-the-mechanism-of-action-of-serotonin-in-human-adrenocortical-cells
#16
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
https://www.readbyqxmd.com/read/27727448/impaired-calcium-mobilization-in-natural-killer-cells-from-chronic-fatigue-syndrome-myalgic-encephalomyelitis-patients-is-associated-with-transient-receptor-potential-melastatin-3-ion-channels
#17
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 protein expression has been identified in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca(2+) mobilization has yet to be determined. Fifteen CFS/ME patients (mean age 48·82 ± 9·83 years) and 25 healthy controls (mean age 39·2 ± 12·12 years) were examined. Isolated natural killer (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
https://www.readbyqxmd.com/read/27718503/immunohistochemical-analysis-of-t-type-calcium-channels-in-acquired-melanocytic-nevi-and-melanoma
#18
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
https://www.readbyqxmd.com/read/27713840/in-silico-identification-of-t-type-calcium-channel-blockers-a-ligand-based-pharmacophore-mapping-approach
#19
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
https://www.readbyqxmd.com/read/27696904/investigational-calcium-channel-blockers-for-the-treatment-of-hypertension
#20
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
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