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T-type calcium channel

Lina A Matschke, Susanne Rinné, Terrance P Snutch, Wolfgang H Oertel, Amalia M Dolga, Niels Decher
The physiological, intrinsic activity of noradrenergic locus coeruleus (LC) neurons is important for the control of sleep/wakefulness, cognition and autonomous body functions. Dysregulations of the LC-noradrenergic network contribute to the pathogenesis of psychiatric disorders and are key findings in early stages of neurodegenerative diseases. Therefore, identifying ion channels mediating the intrinsic pacemaking mechanism of LC neurons, which is in turn directly coupled to Ca2+ homeostasis and cell survival signaling pathways, can help to foster our understanding of the vulnerability of these neurons in neurodegenerative diseases...
March 7, 2018: Molecular and Cellular Neurosciences
Alessandra Romanelli, Alessandra Affinito, Concetta Avitabile, Silvia Catuogno, Paola Ceriotti, Margherita Iaboni, Jessica Modica, Geroloma Condorelli, Daniele Catalucci
Small therapeutic peptides represent a promising field for the treatment of pathologies such as cardiac diseases. However, the lack of proper target-selective carriers hampers their translation towards a potential clinical application. Aptamers are cell-specific carriers that bind with high affinity to their specific target. However, some limitations on their conjugation to small peptides and the functionality of the resulting aptamer-peptide chimera exist. Here, we generated a novel aptamer-peptide chimera through conjugation of the PDGFRβ-targeting Gint4...
2018: PloS One
Minglin Pan, Ying Han, Aninda Basu, Anzhi Dai, Rui Si, Conor Willson, Angela Balistrieri, Brian T Scott, Ayako Makino
Coronary microvascular rarefaction due to endothelial cell (EC) dysfunction is one of the causes of increased morbidity and mortality in diabetes. Coronary ECs in diabetes are more apoptotic due partly to mitochondrial calcium overload. This study was designed to investigate the role of hexokinase 2 (HK2, an endogenous inhibitor of voltage-dependent anion channel) in coronary endothelial dysfunction in type 2 diabetes. We used mouse coronary ECs (MCECs) isolated from type 2 diabetic mice and human coronary ECs (HCECs) from type 2 diabetic patients to examine protein levels and mitochondrial functions...
March 7, 2018: American Journal of Physiology. Cell Physiology
Yumeng Chen, Yaling Shen, Wei Wang, Dongzhi Wei
Background: The filamentous fungus Trichoderma reesei Rut-C30 is one of the most vital fungi for the production of cellulases, which can be used for biofuel production from lignocellulose. Nevertheless, the mechanism of transmission of external stimuli and signals in modulating cellulase production in T. reesei Rut-C30 remains unclear. Calcium is a known second messenger regulating cellulase gene expression in T. reesei . Results: In this study, we found that a biologically relevant extracellular Mn2+ concentration markedly stimulates cellulase production, total protein secretion, and the intracellular Mn2+ concentration of Rut-C30, a cellulase hyper-producing strain of T...
2018: Biotechnology for Biofuels
Katharina T Schrapers, Gerhard Sponder, Franziska Liebe, Hendrik Liebe, Friederike Stumpff
Absorption of ammonia from the gastrointestinal tract results in problems that range from hepatic encephalopathy in humans to poor nitrogen efficiency of cattle with consequences for the global climate. Previous studies on epithelia and cells from the native ruminal epithelium suggest functional involvement of the bovine homologue of TRPV3 (bTRPV3) in ruminal NH4+ transport. Since the conductance of TRP channels to NH4+ has never been studied, bTRPV3 was overexpressed in HEK-293 cells and investigated using the patch-clamp technique and intracellular calcium imaging...
2018: PloS One
Aleksi Suo, Allison Childers, Adrijana D'Silva, Lars F Petersen, Shannon Otsuka, Michelle Dean, Haocheng Li, Emeka K Enwere, Brant Pohorelic, Alexander Klimowicz, Ivana A Souza, Jawed Hamid, Gerald W Zamponi, DGwyn Bebb
Introduction: Voltage-gated calcium channels (VGCC) have been found to be differentially expressed in several different tumor types, but their role in tumor growth, malignant invasion, metastases and impact on clinical outcomes has not been clarified. Materials and Methods: From a cohort database of 193 patients with early-stage NSCLC, 163 formalin-fixed paraffin-embedded specimens were available for analysis to construct tissue microarrays. Cav3.1 protein expression was detected using fluorescence immunohistochemistry, and quantified using automated image acquisition and analysis...
February 2, 2018: Oncotarget
F Xin, H Huang, P Liu, J Ren, S Zhang, Y Cheng, W Wang
BACKGROUND: Muscarinic acetylcholine receptor (mAChR) activation is an important factor to enhance the motility of gastrointestinal (GI) smooth muscle. Large conductance Ca2+ -activated potassium (BK) channels are widely expressed in GI smooth muscle. Roles of BK in carbachol (a mAChR agonist) induced enhancement of GI motility and the molecular mechanisms remains unknown and were investigated in this study. METHODS: Colonic smooth muscle (CSM) strip was perfused to record motility in vitro...
February 28, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Ana Laura Sanchez-Sandoval, Zazil Herrera Carrillo, Clara Estela Díaz Velásquez, Dulce María Delgadillo, Heriberto Manuel Rivera, Juan Carlos Gomora
Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30-40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3...
2018: PloS One
Wen Chen, Ye-Nan Chi, Xue-Jing Kang, Qing-Ying Liu, Hao-Lin Zhang, Zhi-Hua Li, Zi-Fang Zhao, Yin Yang, Li Su, Jie Cai, Fei-Fei Liao, Ming Yi, You Wan, Feng-Yu Liu
Injuries to peripheral nerve fibers induce neuropathic pain. But the involvement of adjacent uninjured fibers to pain is not fully understood. The present study aims to investigate the possible contribution of Cav 3.2 T-type calcium channels in uninjured afferent nerve fibers to neuropathic pain in rats with spared nerve injury (SNI). Aβ-, Aδ- and C-fibers of the uninjured sural nerve were sensitized revealed by in vivo single-unit recording, which were accompanied by accumulation of Cav 3.2 T-type calcium channel proteins shown by Western blotting...
2018: Frontiers in Molecular Neuroscience
Stuart M Cain, John R Tyson, Hyun-Beom Choi, Rebecca Ko, Paulo J C Lin, Jeffrey M LeDue, Kim L Powell, Louis-Philippe Bernier, Ravi L Rungta, Yi Yang, Pieter R Cullis, Terence J O'Brien, Brian A MacVicar, Terrance P Snutch
OBJECTIVE: Genetic alterations have been identified in the CACNA1H gene, encoding the CaV 3.2 T-type calcium channel in patients with absence epilepsy, yet the precise mechanisms relating to seizure propagation and spike-wave-discharge (SWD) pacemaking remain unknown. Neurons of the thalamic reticular nucleus (TRN) express high levels of CaV 3.2 calcium channels, and we investigated whether a gain-of-function mutation in the Cacna1h gene in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) contributes to seizure propagation and pacemaking in the TRN...
February 21, 2018: Epilepsia
Tamara Timic Stamenic, Slobodan M Todorovic
The central medial nucleus (CeM) is a part of the intralaminar thalamus, which is involved in the control of arousal and sensory processing. However, ionic conductances and mechanisms that regulate the activity of the CeM are not well studied. Here, we used in vitro electrophysiology in acute brain slices from adolescent rats to demonstrate that T-type calcium currents (T-currents) are prominent in the majority of the studied CeM neurons and are critical determinants of low-threshold calcium spikes (LTSs), which in turn regulate excitability of these neurons...
January 2018: ENeuro
Ji-Woon Kim, Hyun Ah Oh, Sung Hoon Lee, Ki Chan Kim, Pyung Hwa Eun, Mee Jung Ko, Edson Luck T Gonzales, Hana Seung, Seonmin Kim, Geon Ho Bahn, Chan Young Shin
T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3...
February 21, 2018: Biomolecules & Therapeutics
Yan Yang, Yihui Cui, Kangning Sang, Yiyan Dong, Zheyi Ni, Shuangshuang Ma, Hailan Hu
The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine...
February 14, 2018: Nature
H Kaya, B Polat, A Albayrak, T Mercantepe, B Buyuk
Paracetamol (P), one of the most popular and commonly used analgesic and antipyretic agents, causes hepatotoxicity in overdoses. Amlodipine (AML), an L-type calcium channel blocker, has been shown to have anti-inflammatory activity by reversing the effect of calcium in the inflammation pathogenesis. In this study, the hepatoprotective activity of AML on P-induced hepatotoxicity was evaluated. Thirty male albino Wistar rats were divided into five groups: (1) control, (2) 2 g/kg of P, (3) 2 g/kg of P + 5 mg/kg of AML, (4) 2 g/kg of P + 10 mg/kg of AML, and (5) 10 mg/kg of AML...
January 1, 2018: Human & Experimental Toxicology
Nicholas C Vierra, Matthew T Dickerson, Kelli L Jordan, Prasanna K Dadi, Ketaki A Kadare, Molly K Altman, Sarah C Milian, David A Jacobson
OBJECTIVE: Single-cell RNA sequencing studies have revealed that the type-2 diabetes associated two-pore domain K+ (K2P) channel TALK-1 is abundantly expressed in somatostatin-secreting δ-cells. However, a physiological role for TALK-1 in δ-cells remains unknown. We previously determined that in β-cells, K+ flux through endoplasmic reticulum (ER)-localized TALK-1 channels enhances ER Ca2+ leak, modulating Ca2+ handling and insulin secretion. As glucose amplification of islet somatostatin release relies on Ca2+-induced Ca2+ release (CICR) from the δ-cell ER, we investigated whether TALK-1 modulates δ-cell Ca2+ handling and somatostatin secretion...
January 31, 2018: Molecular Metabolism
O Maiques, C Barceló, A Panosa, J Pijuan, J L Orgaz, I Rodriguez-Hernandez, C Matas-Nadal, G Tell, R Vilella, A Fabra, Puig S, V Sanz-Moreno, X Matias-Guiu, C Canti, J Herreros, R M Marti, A Macià
Melanoma is a malignant tumor derived from melanocytes. Once disseminated, it is usually highly resistant to chemotherapy and is associated with poor prognosis. We have recently reported that T-type calcium channels (TTCCs) are overexpressed in melanoma cells and play an important role in melanoma progression. Importantly, TTCC pharmacological blockers reduce proliferation and deregulate autophagy leading to apoptosis. Here, we analyze the role of autophagy during migration/invasion of melanoma cells. TTCC Cav3...
January 31, 2018: Pigment Cell & Melanoma Research
Alexander R Kent, Xiaoyi Min, Quinn H Hogan, Jeffery M Kramer
OBJECTIVE: The mechanisms of dorsal root ganglion (DRG) stimulation for chronic pain remain unclear. The objective of this work was to explore the neurophysiological effects of DRG stimulation using computational modeling. METHODS: Electrical fields produced during DRG stimulation were calculated with finite element models, and were coupled to a validated biophysical model of a C-type primary sensory neuron. Intrinsic neuronal activity was introduced as a 4 Hz afferent signal or somatic ectopic firing...
January 29, 2018: Neuromodulation: Journal of the International Neuromodulation Society
Yu Zhu, Liao-Bin Dong, Zhi-Jun Zhang, Min Fan, Qin-Feng Zhu, Yan-Yan Qi, Yu-Chen Liu, Li-Yan Peng, Xing-De Wu, Qin-Shi Zhao
Three new Lycopodium alkaloids (1-3), together with 15 known alkaloids, were isolated from club moss Lycopodium japonicum. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR spectra. Compound 1 has an unusual β-oriented methyl group substituted at C-15 and an α-hydroxy cyclopentenone moiety. All new alkaloids were evaluated for the inhibition of T-type calcium channel.
January 26, 2018: Journal of Asian Natural Products Research
Alan J Garber, Martin J Abrahamson, Joshua I Barzilay, Lawrence Blonde, Zachary T Bloomgarden, Michael A Bush, Samuel Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Vivian A Fonseca, Jeffrey R Garber, W Timothy Garvey, George Grunberger, Yehuda Handelsman, Irl B Hirsch, Paul S Jellinger, Janet B McGill, Jeffrey I Mechanick, Paul D Rosenblit, Guillermo E Umpierrez
A1C = hemoglobin A1C; AACE = American Association of Clinical Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure; ACEI = angiotensin-converting enzyme inhibitor; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AGI = alpha-glucosidase inhibitor; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BAS = bile acid sequestrant; BCR-QR = bromocriptine quick release; BMI = body mass index; BP = blood pressure; CCB = calcium channel blocker; CHD = coronary heart disease; CKD = chronic kidney disease; CVD = cardiovascular disease; DASH = Dietary Approaches to Stop Hypertension; DPP4 = dipeptidyl peptidase 4; eGFR = estimated glomerular filtration rate; ER = extended release; FDA = Food and Drug Administration; GLP1 = glucagon-like peptide 1; HDL-C = high-density lipoprotein cholesterol; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C = low-density lipoprotein cholesterol; LDL-P = low-density lipoprotein particle; Look AHEAD = Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA = obstructive sleep apnea; RCT = randomized controlled trial; SU = sulfonylurea; SGLT2 = sodium glucose cotransporter-2; SMBG = self-monitoring of blood glucose; T2D = type 2 diabetes; TZD = thiazolidinedione; VADT = Veterans Affairs Diabetes Trial...
January 2018: Endocrine Practice
Sirinart Kumfu, Juthamas Khamseekaew, Siripong Palee, Somdet Srichairatanakool, Suthat Fucharoen, Siriporn C Chattipakorn, Nipon Chattipakorn
Although both iron chelators and T-type calcium channel (TTCC) blockers have been shown to exert cardioprotection by decreasing cardiac iron deposition and reducing left ventricular (LV) dysfunction via different channels in iron-overloaded rodent models, the cardioprotective effects of combined iron chelator and TTCC blocker treatment in thalassemic mice has not been investigated. We hypothesized that a combined iron chelator and TTCC blocker exerts better cardioprotection than monotherapy by decreasing cardiac iron accumulation, apoptosis and oxidative stress...
January 18, 2018: European Journal of Pharmacology
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