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Voltage-dependent calcium channels

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https://www.readbyqxmd.com/read/27899270/limitations-in-electrophysiological-model-development-and-validation-caused-by-differences-between-simulations-and-experimental-protocols
#1
REVIEW
Jesús Carro, José F Rodríguez-Matas, Violeta Monasterio, Esther Pueyo
Models of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived markers. Although this procedure reduces the uncertainty in the calculation of conductances, many studies evaluate electrophysiological AP-derived markers from single cell simulations, whereas experimental measurements are obtained from tissue preparations...
November 27, 2016: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/27889432/decrease-of-high-voltage-ca-2-currents-in-the-dentate-gyrus-granule-cells-by-entorhinal-amyloidopathy-is-reversed-by-calcium-channel-blockade
#2
Hamid Gholami Pourbadie, Nima Naderi, Hadi Mirzapour Delavar, Mahshid Hosseinzadeh, Nasrin Mehranfard, Fariba Khodagholi, Mahyar Janahmadi, Fereshteh Motamedi
In the Alzheimer's disease (AD), entorhinal-hippocampal circuit is one of the earliest affected networks. There are some evidences indicating abnormal neuronal excitability and impaired synaptic plasticity in the dentate gyrus (DG) of AD animal model. However, the underlying mechanism leading to DG dysfunction particularly in the early phase of AD is not known. Since calcium dyshomeostasis has a critical role in the etiology of AD, it is possible that this phenomenon precedes electrophysiological alteration in the DG...
November 24, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27877916/study-of-local-intracellular-signals-regulating-axonal-morphogenesis-using-a-microfluidic-device
#3
Daiki Uryu, Tomohiro Tamaru, Azusa Suzuki, Rie Sakai, Yoshiyuki Konishi
The establishment and maintenance of axonal patterning is crucial for neuronal function. To identify the molecular systems that operate locally to control axonal structure, it is important to manipulate molecular functions in restricted subcellular areas for a long period of time. Microfluidic devices can be powerful tools for such purposes. In this study, we demonstrate the application of a microfluidic device to clarify the function of local Ca(2+) signals in axons. Membrane depolarization significantly induced axonal branch-extension in cultured cerebellar granule neurons (CGNs)...
2016: Science and Technology of Advanced Materials
https://www.readbyqxmd.com/read/27872869/dynamic-association-of-calcium-channel-subunits-at-the-cellular-membrane
#4
Andreas Voigt, Romy Freund, Jennifer Heck, Markus Missler, Gerald J Obermair, Ulrich Thomas, Martin Heine
High voltage gated calcium channels (VGCCs) are composed of at least three subunits, one pore forming [Formula: see text]-subunit, an intracellular [Formula: see text]-variant, and a mostly extracellular [Formula: see text]-variant. Interactions between these subunits determine the kinetic properties of VGCCs. It is unclear whether these interactions are stable over time or rather transient. Here, we used single-molecule tracking to investigate the surface diffusion of [Formula: see text]- and [Formula: see text]-subunits at the cell surface...
October 2016: Neurophotonics
https://www.readbyqxmd.com/read/27864509/loss-of-%C3%AE-adrenergic-stimulated-phosphorylation-of-cav1-2-channels-on-ser1700-leads-to-heart-failure
#5
Linghai Yang, Dao-Fu Dai, Can Yuan, Ruth E Westenbroek, Haijie Yu, Nastassya West, Horacio O de la Iglesia, William A Catterall
L-type Ca(2+) currents conducted by voltage-gated calcium channel 1.2 (CaV1.2) initiate excitation-contraction coupling in the heart, and altered expression of CaV1.2 causes heart failure in mice. Here we show unexpectedly that reducing β-adrenergic regulation of CaV1.2 channels by mutation of a single PKA site, Ser1700, in the proximal C-terminal domain causes reduced contractile function, cardiac hypertrophy, and heart failure without changes in expression, localization, or function of the CaV1.2 protein in the mutant mice (SA mice)...
November 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27861914/a-unifying-hypothesis-for-m1-muscarinic-receptor-signalling-in-pyramidal-neurons
#6
Sameera Dasari, Corey Hill, Allan T Gulledge
Gq -coupled muscarinic acetylcholine (ACh) receptors (mAChRs) mediate two distinct electrophysiological responses in cortical pyramidal neurons: transient inhibition driven by calcium-dependent small conductance potassium ("SK") channels, and longer-lasting and voltage-dependent excitation involving non-specific cation channels. Here we examine the interaction of these two cholinergic responses with respect to their contributions to intracellular calcium dynamics, testing the unifying hypothesis that rundown of inhibitory SK responses at resting membrane potentials (RMPs) reflects depletion of intracellular calcium stores, while mAChR-driven excitation acts to refill those stores by promoting voltage-dependent entry of extracellular calcium...
November 12, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27859782/inhibition-of-the-mitochondrial-calcium-uniporter-mcu-rescues-dopaminergic-neurons-in-pink1-zebrafish
#7
Smijin Soman, Marcus Keatinge, Mahsa Moein, Marc DaCosta, Heather Mortiboys, Alexander Skupin, Sreedevi Sugunan, Michal Bazala, Jacek Kuznicki, Oliver Bandmann
Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of early onset Parkinson's disease (PD). Loss of PINK1 function causes dysregulation of mitochondrial calcium homeostasis, resulting in mitochondrial dysfunction and neuronal cell death. We report that both genetic and pharmacological inactivation of the mitochondrial calcium uniporter (MCU), located in the inner mitochondrial membrane, prevents dopaminergic neuronal cell loss in pink1(Y431) * mutant zebrafish (Danio rerio) via rescue of mitochondrial respiratory chain function...
November 12, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27859335/extracellular-protons-enable-activation-of-the-calcium-dependent-chloride-channel-tmem16a-ano1
#8
Silvia Cruz-Rangel, José J De Jesus-Pérez, Iván A Aréchiga-Figueroa, Aldo A Rodríguez-Menchaca, Patricia Pérez-Cornejo, H Criss Hartzell, Jorge Arreola
TMEM16A (ANO1), the pore forming subunit of a Ca(2+) -dependent Cl(-) channel (CaCC), is activated by direct, voltage-dependent, binding of intracellular Ca(2+) . Endogenous CaCCs are regulated by extracellular protons; however, the molecular basis of such regulation remains unidentified. Here, we evaluated the effects of different extracellular proton concentrations ([H(+) ]o ) on mouse TMEM16A expressed in HEK-293 cells using whole-cell and inside-out patch clamp recordings. We found that increasing the [H(+) ]o from 10(-10) to 10(-5...
November 17, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27857685/conditional-knockout-of-cav2-1-disrupts-the-accuracy-of-spatial-recognition-of-ca1-place-cells-and-spatial-contextual-recognition-behavior
#9
Dahee Jung, Yu J Hwang, Hoon Ryu, Masanobu Kano, Kenji Sakimura, Jeiwon Cho
Hippocampal pyramidal neurons play an essential role in processing spatial information as implicated with its place-dependent firing. Although, previous slice physiology studies have reported that voltage gated calcium channels contribute to spike shapes and corresponding firing rate in the hippocampus, the roles of P/Q type calcium channels (Cav2.1) underlying neural activity in behaving mice have not been well-investigated. To determine physiological and behavioral roles of Cav2.1, we conducted place cell recordings in CA1 and hippocampus dependent learning/memory tasks using mice lacking Cav2...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27853054/expression-of-cyp11b2-in-aldosterone-producing-adrenocortical-adenoma-regulatory-mechanisms-and-clinical-significance
#10
Yasuhiro Nakamura, Yuto Yamazaki, Yuta Tezuka, Fumitoshi Satoh, Hironobu Sasano
Aldosterone-producing adrenocortical adenoma (APA) is responsible for the majority of cases clinically diagnosed as primary aldosteronism. Aldosterone synthase (CYP11B2) is one of the enzymes that play essential roles in aldosterone synthesis and is involved in the pathogenesis of APA. Recent studies have demonstrated that various factors and regulators influence the expression and function of CYP11B2 in APA. In particular, somatic mutations, such as gain-of-function and loss-of-function mutations, have been identified in several genes, each of which encodes a pivotal protein that affects the calcium signaling pathway, the expression of CYP11B2, and aldosterone production...
2016: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27852936/the-vasorelaxant-mechanisms-of-methanol-on-isolated-rat-aortic-rings-involvement-of-ion-channels-and-signal-transduction-pathways
#11
Y Bai, Q Zhang, Z Yang, Z Meng, Q Zhao
It is reported that methanol is generally used as an industrial solvent, antifreeze, windshield washer fluid, cooking fuel and perfume. Methanol ingestion can lead to severe metabolic disturbances, blindness, or even death. So far, few studies about its negative effects on cardiovascular system have been reported. The purpose of this study was to determine the vasoactive effect of methanol and roles of ion channels and signal transduction pathways on isolated rat aorta. The results suggested that the mechanism of methanol-induced vasorelaxation at low concentrations (<500 mM) was mediated by ATP-sensitive K(+) (KATP) and L-type Ca(2+) channels, but the mechanism at high concentrations (>600 mM) was related to KATP, voltage-dependent K(+), big-conductance Ca(2+)-activated K(+), L-type Ca(2+) channels as well as prostacyclin, protein kinase C, β-adrenoceptors pathways...
November 16, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27848217/pregabalin-for-the-treatment-of-drug-and-alcohol-withdrawal-symptoms-a-comprehensive-review
#12
REVIEW
Rainer Freynhagen, Miroslav Backonja, Stephan Schug, Gavin Lyndon, Bruce Parsons, Stephen Watt, Regina Behar
Treatments for physical dependence and associated withdrawal symptoms following the abrupt discontinuation of prescription drugs (such as opioids and benzodiazepines), nicotine, alcohol, and cannabinoids are available, but there is still a need for new and more effective therapies. This review examines evidence supporting the potential use of pregabalin, an α2δ voltage-gated calcium channel subunit ligand, for the treatment of physical dependence and associated withdrawal symptoms. A literature search of the MEDLINE and Cochrane Library databases up to and including 11 December 2015 was conducted...
November 16, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27826409/the-relaxant-effect-of-the-montivipera-bornmuelleri-snake-venom-on-vascular-contractility
#13
Claudine Accary, Souad Hraoui-Bloquet, Riyad Sadek, Asma Alameddine, Ziad Fajloun, Jean-Claude Desfontis, Yassine Mallem
Molecular richness of snake venoms is an important source of proteins and toxins with potent effects on the cardiovascular system. The alteration of the vascular system in the victim after a venomous snake bite is usually expressed by a significant decrease in blood pressure. Therefore, exploring snake venom to extract and characterize its biomolecules is of considerable medical interest, and formed the basis of this study. We assessed the potential of the venom of Montivipera bornmuelleri, a viper from Lebanon, to induce relaxant effect on isolated Wistar rat aorta via several mechanisms of action...
2016: Journal of Venom Research
https://www.readbyqxmd.com/read/27826078/participation-of-potassium-channels-in-the-antinociceptive-effect-of-docosahexaenoic-acid-in-the-rat-formalin-test
#14
Arizai Yolia Landa-Juárez, Mario I Ortiz, Gilberto Castañeda-Hernández, Aracely Evangelina Chávez-Piña
Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that has shown gastroprotective, cardioprotective, neuroprotective, anti-inflammatory and antinociceptive effects in different models. However, its action mechanism is still not well-defined. Reports indicate that some PUFAs regulate potassium (K(+)) channels in ventricular myocytes of rodents. As a result, the aim of this study was to evaluate the probable participation of K(+) channels in the antinociceptive effect of DHA. The rat paw 1% formalin test was used to assess nociception and antinociception...
November 6, 2016: European Journal of Pharmacology
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
#15
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/27799552/calcium-sensor-regulation-of-the-cav2-1-ca2-channel-contributes-to-long-term-potentiation-and-spatial-learning
#16
Evanthia Nanou, Todd Scheuer, William A Catterall
Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated Ca(2+) type 2.1 (CaV2.1) channels. However, the contribution of regulation of CaV2.1 channels to other forms of neuroplasticity and to learning and memory are not known. Here we have studied mice with a mutation (IM-AA) that disrupts regulation of CaV2.1 channels by calmodulin and related calcium sensor proteins. Surprisingly, we find that long-term potentiation (LTP) of synaptic transmission at the Schaffer collateral-CA1 synapse in the hippocampus is substantially weakened, even though this form of synaptic plasticity is thought to be primarily generated postsynaptically...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27799318/independent-activation-of-ion-conduction-pores-in-the-double-barreled-calcium-activated-chloride-channel-tmem16a
#17
Novandy K Lim, Andy K M Lam, Raimund Dutzler
The TMEM16 proteins constitute a family of membrane proteins with unusual functional breadth, including lipid scramblases and Cl(-) channels. Members of both these branches are activated by Ca(2+), acting from the intracellular side, and probably share a common architecture, which was defined in the recent structure of the lipid scramblase nhTMEM16. The structural features of subunits and the arrangement of Ca(2+)-binding sites in nhTMEM16 suggest that the dimeric protein harbors two locations for catalysis that are independent with respect to both activation and lipid conduction...
November 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27798183/%C3%AE-2%C3%AE-2-controls-the-function-and-trans-synaptic-coupling-of-cav1-3-channels-in-mouse-inner-hair-cells-and-is-essential-for-normal-hearing
#18
Barbara Fell, Stephanie Eckrich, Kerstin Blum, Tobias Eckrich, Dietmar Hecker, Gerald J Obermair, Stefan Münkner, Veit Flockerzi, Bernhard Schick, Jutta Engel
: The auxiliary subunit α2δ2 modulates the abundance and function of voltage-gated calcium channels. Here we show that α2δ2 mRNA is expressed in neonatal and mature hair cells. A functional α2δ2-null mouse, the ducky mouse (du), showed elevated auditory brainstem response click and frequency-dependent hearing thresholds. Otoacoustic emissions were not impaired pointing to normal outer hair cell function. Peak Ca(2+) and Ba(2+) currents of mature du/du inner hair cells (IHCs) were reduced by 30-40%, respectively, and gating properties, such as the voltage of half-maximum activation and voltage sensitivity, were altered, indicating that Cav1...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27793988/crispr-cas9-mediated-endogenous-c-terminal-tagging-of-trypanosoma-cruzi-genes-reveals-the-acidocalcisome-localization-of-the-inositol-1-4-5-trisphosphate-receptor
#19
Noelia Lander, Miguel A Chiurillo, Melissa Storey, Anibal E Vercesi, Roberto Docampo
Methods for genetic manipulation of Trypanosoma cruzi, the etiologic agent of Chagas disease, have been highly inefficient, and no endogenous tagging of genes has been reported to date. We report here the use of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated gene 9) system for endogenously tagging genes in this parasite. The utility of the method was established by tagging genes encoding proteins of known localization such as TcFCaBP (flagellar calcium binding protein) and TcVP1 (vacuolar proton pyrophosphatase), and two proteins of undefined or disputed localization, the TcMCU (mitochondrial calcium uniporter) and TcIP3R (inositol 1,4,5-trisphosphate receptor)...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27787949/pasireotide-prevents-nuclear-factor-of-activated-t-cells-nuclear-translocation-and-acts-as-a-protective-agent-in-aminoglycoside-induced-auditory-hair-cell-loss
#20
Daniel Bodmer, Adrijana Perkovic, Marijana Sekulic-Jablanovic, Matthew B Wright, Vesna Petkovic
Hearing impairment is a global health problem with a high socioeconomic impact. Damage to auditory hair cells (HCs) in the inner ear as a result of aging, disease, trauma, or toxicity, underlies the majority of cases of sensorineural hearing loss. Previously we demonstrated that the Ca(2+) -sensitive neuropeptide, somatostatin (SST), and an analog, octreotide, protect HCs from gentamicin-induced cell death in vitro. Aminoglycosides such as gentamicin trigger a calcium ion influx (Ca(2+) ) that activates pro-apoptotic signaling cascades in HCs...
October 27, 2016: Journal of Neurochemistry
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