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Voltage-gated calcium channels

Neivys García-Delgado, Myrian Velasco, Carmen Sánchez-Soto, Carlos Manlio Díaz-García, Marcia Hiriart
Pancreatic beta cells during the first month of development acquire functional maturity, allowing them to respond to variations in extracellular glucose concentration by secreting insulin. Changes in ionic channel activity are important for this maturation. Within the voltage-gated calcium channels (VGCC), the most studied channels are high-voltage-activated (HVA), principally L-type; while low-voltage-activated (LVA) channels have been poorly studied in native beta cells. We analyzed the changes in the expression and activity of VGCC during the postnatal development in rat beta cells...
2018: Frontiers in Endocrinology
Sana Amhimmid Badr, Maryan Waheeb Fahmi, Manal Mahmoud Nomir, Mamdouh Mohammad El-Shishtawy
Objective: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. The identification of new simple, inexpensive and highly accurate markers for HCC diagnosis and screening is needed. This case-control study evaluates the role of annexin A2 and voltage-gated calcium channels α2δ1 subunit as serum biomarkers for HCC diagnosis. Methods: The study comprised three groups: group 1, 50 patients with an initial diagnosis of HCC associated with chronic hepatitis C virus infection; group 2, 25 patients diagnosed with chronic hepatitis C virus infection and cirrhosis without any evidence of HCC; and group 3, 15 healthy controls...
February 2018: Cancer Biology & Medicine
Bailin Liu, Ruixiu Shi, Xiang Li, Yanping Liu, Xueqin Feng, Xueyi Chen, Xiaorong Fan, Yingying Zhang, Wenna Zhang, Jiaqi Tang, Xiuwen Zhou, Na Li, Xiyuan Lu, Zhice Xu
BACKGROUND: Prenatal hypoxia is suggested to be associated with increased risks of hypertension in offspring. This study tested whether prenatal hypoxia resulted in salt-sensitive offspring and its related mechanisms of vascular ion channel remodeling. METHODS AND RESULTS: Pregnant rats were housed in a normoxic (21% O2 ) or hypoxic (10.5% O2 ) chamber from gestation days 5 to 21. A subset of male offspring received a high-salt diet (8% NaCl) from 4 to 12 weeks after birth...
March 15, 2018: Journal of the American Heart Association
Xiaoying Wang, Jiefu Peng, Jing Wang, Miao Li, Di Wu, Songyan Wu, Jipei Liao, Jun Dou
Background: Despite the breadth of understanding the noncoding RNAs' function in molecular biology, their functional roles in hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated the effect of hepatitis C virus (HCV) core upon the expression of noncoding RNAs. Methods: The lncRNAs, mRNAs, and circRNAs were employed for identification of HCV core protein gene expression in human Huh7 hepatoma (Huh7) cell line. In data analysis, we applied a threshold that eliminated all genes that were not increased or decreased by at least a 2-fold change in a comparison between transfected and control cells...
2018: OncoTargets and Therapy
Rahul Banerjee, Jesse B Yoder, David T Yue, L Mario Amzel, Gordon F Tomaselli, Sandra B Gabelli, Manu Ben-Johny
Calmodulin (CaM) regulation of voltage-gated calcium (CaV ) channels is a powerful Ca2+ feedback mechanism that adjusts Ca2+ influx, affording rich mechanistic insights into Ca2+ decoding. CaM possesses a dual-lobed architecture, a salient feature of the myriad Ca2+ -sensing proteins, where two homologous lobes that recognize similar targets hint at redundant signaling mechanisms. Here, by tethering CaM lobes, we demonstrate that bilobal architecture is obligatory for signaling to CaV channels. With one lobe bound, CaV carboxy tail rearranges itself, resulting in a preinhibited configuration precluded from Ca2+ feedback...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jill K Badin, Ayeeshik Kole, Benjamin Stivers, Victor Progar, Anisha Pareddy, Mouhamad Alloosh, Michael Sturek
BACKGROUND: There is a preponderance of evidence implicating diabetes with increased coronary artery disease (CAD) and calcification (CAC) in human patients with metabolic syndrome (MetS), but the effect of diabetes on CAD severity in animal models remains controversial. We investigated whether diabetes exacerbates CAD/CAC and intracellular free calcium ([Ca2+ ]i ) dysregulation in the clinically relevant Ossabaw miniature swine model of MetS. METHODS: Sixteen swine, eight with alloxan-induced diabetes, were fed a hypercaloric, atherogenic diet for 6 months...
March 9, 2018: Journal of Translational Medicine
Kevin S O'Connell, Nathaniel W McGregor, Christine Lochner, Robin Emsley, Louise Warnich
Considerable evidence suggests that autism spectrum disorders (ASD), schizophrenia (SCZ), bipolar disorder (BD) and obsessive-compulsive disorder (OCD) share a common molecular aetiology, despite their unique clinical diagnostic criteria. The aim of this study was therefore to determine and characterise the common and unique molecular architecture of ASD, SCZ, BD and OCD. Gene lists were obtained from previously published studies for ASD, BD, SCZ and for OCD. Genes identified to be common to all disorders, or unique to one specific disorder, were included for enrichment analyses using the web-server tool Enrichr...
March 2, 2018: Molecular and Cellular Neurosciences
Kimberley J Billingsley, Maurizio Manca, Olympia Gianfrancesco, David A Collier, Helen Sharp, Vivien J Bubb, John P Quinn
Genomic wide association studies identified the CACNA1C locus as genetically associated with both schizophrenia and bipolar affective disorder. CACNA1C encodes Cav1.2, one of four subunits of L-type voltage gated calcium channels. Variation resides in non-coding regions of CACNA1C which interact with the promoter and are validated expression quantitative trait loci. Using reporter gene constructs we demonstrate the CACNA1C promoter is a major mediator of inducible regulation of CACNA1C activity in the SH-SY5Y neuroblastoma cell line...
February 28, 2018: Schizophrenia Research
Kunsala T D S Yapa, Jennifer Deuis, Amelia A Peters, Paraic A Kenny, Sarah J Roberts-Thomson, Irina Vetter, Gregory R Monteith
AIMS: To assess levels of the calcium permeable transient receptor potential cation channel, subfamily melastatin, member 8 (TRPM8) in breast cancer molecular subtypes and to assess the consequences of TRPM8 pharmacological inhibition with AMTB (an inhibitor of TRPM8) on breast cancer cell lines. MATERIALS AND METHODS: Cell viability and migration of breast cancer cells was determined using MTS assays and wound healing assays, respectively. RNA-Seq analysis of breast tumours and qPCR in breast cancer cell lines were used to assess mRNA levels of ion channels...
February 26, 2018: Life Sciences
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
Mena Abdelsayed, Manpreet Ruprai, Peter C Ruben
E1784K is the most common mixed syndrome SCN5a mutation underpinning both Brugada syndrome type 1 (BrS1) and Long-QT syndrome type 3 (LQT3). The charge reversal mutant enhances the late sodium current (INa ) passed by the cardiac voltage-gated sodium channel (NaV 1.5), delaying cardiac repolarization. Exercise-induced triggers, like elevated temperature and cytosolic calcium, exacerbate E1784K late INa . In this study, we tested the effects of Ranolazine, the late INa blocker, on voltage-dependent and kinetic properties of E1784K at elevated temperature and cytosolic calcium...
February 26, 2018: Scientific Reports
Lilian R Ferreira Faro, Miguel Alfonso, Vania Moraes Ferreira, Rafael Durán
The possible role of voltage-sensitive calcium channels (VSCC) activation on the HgCl2 -induced dopamine release was investigated using selective VSCC blockers and the dopamine levels were measured by HPLC from samples obtained by in vivo brain microdialysis. Infusion of HgCl2 in nicardipine (10 or 100 μM) or flunaricine (10 μM) pretreated animals had no significant effect on dopamine release induced by HgCl2 . Pretreatment with 100 μM flunaricine, 20 μM ω-conotoxin MVIIC, or ω-conotoxin GVIA significantly decreased the HgCl2 -induced dopamine release over 61%, 88%, and 99%, respectively...
February 12, 2018: Environmental Toxicology and Pharmacology
Vera Geraldes, Sérgio Laranjo, Isabel Rocha
Hypertension is a prevalent and major health problem, involving a complex integration of different organ systems, including the central nervous system (CNS). The CNS and the hypothalamus in particular are intricately involved in the pathogenesis of hypertension. In fact, evidence supports altered hypothalamic neuronal activity as a major factor contributing to increased sympathetic drive and increased blood pressure. Several mechanisms have been proposed to contribute to hypothalamic-driven sympathetic activity, including altered ion channel function...
February 26, 2018: Current Hypertension Reports
Christian J Peters, John M Gilchrist, Jason Tien, Neville P Bethel, Lijun Qi, Tingxu Chen, Lynn Wang, Yuh Nung Jan, Michael Grabe, Lily Y Jan
Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating...
February 16, 2018: Neuron
Ilya Pozdnyakov, Olga Matantseva, Sergei Skarlato
Four-domain voltage-gated cation channels (FVCCs) represent a large family of pseudo-tetrameric ion channels which includes voltage-gated calcium (Cav ) and sodium (Nav ) channels, as well as their homologues. These transmembrane proteins are involved in a wide range of physiological processes, such as membrane excitability, rhythmical activity, intracellular signalling, etc. Information about actual diversity and phylogenetic relationships of FVCCs across the eukaryotic tree of life is scarce. We for the first time performed a taxonomically broad phylogenetic analysis of 277 FVCC sequences from a variety of eukaryotes and showed that many groups of eukaryotic organisms have their own clades of FVCCs...
February 23, 2018: Scientific Reports
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
Jens Ingwersen, Lorenzo De Santi, Britta Wingerath, Jonas Graf, Barbara Koop, Reiner Schneider, Christina Hecker, Friederike Schröter, Mary Bayer, Anna Dorothee Engelke, Michael Dietrich, Philipp Albrecht, Hans-Peter Hartung, Pasquale Annunziata, Orhan Aktas, Tim Prozorovski
Multiple sclerosis (MS) is characterized by inflammatory neurodegeneration, with axonal injury and neuronal cell death occurring in parallel to demyelination. Regarding the molecular mechanisms responsible for demyelination and axonopathy, energy failure, aberrant expression of ion channels and excitotoxicity have been suggested to lead to Ca2+ overload and subsequent activation of calcium-dependent damage pathways. Thus, the inhibition of Ca2+ influx by pharmacological modulation of Ca2+ channels may represent a novel neuroprotective strategy in the treatment of secondary axonopathy...
February 23, 2018: Journal of Neurochemistry
Mónica Rubio Ayala, Tatiana Syrovets, Susanne Hafner, Vitalii Zablotskii, Alexandr Dejneka, Thomas Simmet
Cellular function is modulated by the electric membrane potential controlling intracellular physiology and signal propagation from a motor neuron to a muscle fiber resulting in muscle contraction. Unlike electric fields, magnetic fields are not attenuated by biological materials and penetrate deep into the tissue. We used complex spatiotemporal magnetic fields (17-70 mT) to control intracellular signaling in skeletal muscle cells. By changing different parameters of the alternating magnetic field (amplitude, inversion time, rotation frequency), we induced transient depolarization of cellular membranes leading to i) Na+ influx through voltage-gated sodium channels (VGSC), ii) cytosolic calcium increase, and iii) VGSC- and ryanodine receptor-dependent increase of actin polymerization...
February 16, 2018: Biomaterials
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
Mohamed Chahine
CaV 1.1 channels are organized into four homologous domains (domains I-IV), each composed of a nonpermeable voltage sensor domain (VSD) and a calcium-permeable pore domain. Mutations in the VSD may create a leak and render the VSD permeable to ions. Recording of such a leak current, known as a gating pore current, was hampered by the low expression of these channels in a heterologous expression system. In this issue, Wu et al. (2018. J. Gen. Physiol. show for the first time the biophysical properties of this current using Stac3 to boost the expression of the CaV 1...
February 21, 2018: Journal of General Physiology
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