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https://www.readbyqxmd.com/read/27872869/dynamic-association-of-calcium-channel-subunits-at-the-cellular-membrane
#1
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/27843503/review-cav2-3-r-type-voltage-gated-ca-2-channels-functional-implications-in-convulsive-and-non-convulsive-seizure-activity
#2
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/27823926/cisplatin-induced-neuropathic-pain-is-mediated-by-upregulation-of-n-type-voltage-gated-calcium-channels-in-dorsal-root-ganglion-neurons
#3
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/27725162/the-calcilytics-calhex-231-and-nps-2143-and-the-calcimimetic-calindol-reduce-vascular-reactivity-via-inhibition-of-voltage-gated-ca-2-channels
#4
Harry Z E Greenberg, Kazi S Jahan, Jian Shi, W-S Vanessa Ho, Anthony P Albert
The present study investigates the effect of commonly used negative and positive allosteric modulators of the calcium-sensing receptor (CaSR) on vascular reactivity. In wire myography studies, increasing [Ca(2+)]o from 1mM to 6mM induced concentration-dependent relaxations of methoxamine-induced pre-contracted rabbit mesenteric arteries, with 6mM [Ca(2+)]o producing almost complete relaxation. [Ca(2+)]o-induced relaxations were attenuated in the presence of the calcilytics Calhex-231 and NPS 2143, and abolished by the removal of the endothelium...
November 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27723836/suppression-of-protective-responses-upon-activation-of-l-type-voltage-gated-calcium-channel-in-macrophages-during-mycobacterium-bovis-bcg-infection
#5
Deepika Sharma, Brijendra Kumar Tiwari, Subhash Mehto, Cecil Antony, Gunjan Kak, Yogendra Singh, Krishnamurthy Natarajan
The prevalence of Mycobacterium tuberculosis (M. tb) strains eliciting drug resistance has necessitated the need for understanding the complexities of host pathogen interactions. The regulation of calcium homeostasis by Voltage Gated Calcium Channel (VGCCs) upon M. tb infection has recently assumed importance in this area. We previously showed a suppressor role of VGCC during M. tb infections and recently reported the mechanisms of its regulation by M. tb. Here in this report, we further characterize the role of VGCC in mediating defence responses of macrophages during mycobacterial infection...
2016: PloS One
https://www.readbyqxmd.com/read/27681688/dysregulation-of-calcium-channels-decreases-parasecretion-in-pancreatic-%C3%AE-cells-in-rats-born-small-for-gestational-age
#6
Yan-Yan Jin, Meng-Zao He, Zhen-Yong Wu, Ke Huang, Ying Shen, Li Liang, Jian-Hua Mao
OBJECTIVE: To investigate the role of intrauterine malnourishment in the development and function of pancreatic islet β-cells. METHODS: Whole-cell patch clamping was used to record voltage-gated calcium channel (VGCC)-mediated currents. Insulin secretion was detected by measuring capacitance using a sequence of sine wave stimuli. VGCC currents and insulin secretion were measured in the small for gestational age (SGA) group treated with human recombinant growth hormone (hGH)...
September 29, 2016: Growth Factors
https://www.readbyqxmd.com/read/27633557/calcium-homeostasis-and-protein-kinase-phosphatase-balance-participate-in-nicotine-induced-memory-improvement-in-passive-avoidance-task-in-mice
#7
Agnieszka Michalak, Grazyna Biala
Long-term potentiation (LTP) and long-term depression (LTD) depend on specific postsynaptic Ca(2+)/calmodulin concentration. LTP results from Ca(2+) influx through the activated NMDA receptors or voltage-gated calcium channels (VGCCs) and is linked with activation of protein kinases including mitogen-activated protein kinase (MAPK). Weaker synaptic stimulation, as a result of low Ca(2+) influx, leads to activation of Ca(2+)/calmodulin-dependent phosphatase (calcineurin - CaN) and triggers LTD. Interestingly, both memory formation and drug addiction share similar neuroplastic changes...
September 12, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27577085/mapping-autoantigen-epitopes-molecular-insights-into-autoantibody-associated-disorders-of-the-nervous-system
#8
REVIEW
Nese Sinmaz, Tina Nguyen, Fiona Tea, Russell C Dale, Fabienne Brilot
BACKGROUND: Our knowledge of autoantibody-associated diseases of the central (CNS) and peripheral (PNS) nervous systems has expanded greatly over the recent years. A number of extracellular and intracellular autoantigens have been identified, and there is no doubt that this field will continue to expand as more autoantigens are discovered as a result of improved clinical awareness and methodological practice. In recent years, interest has shifted to uncover the target epitopes of these autoantibodies...
August 30, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27475316/a-case-of-encephalomyeloradiculopathy-in-a-non-carcinomatous-patient-associated-with-p-q-type-voltage-gated-calcium-channel-antibodies
#9
Divpreet Kaur, Divisha Raheja
The presence of P/Q type voltage gated calcium channel (VGCC) antibodies has been strongly correlated with Lambert Eaton Syndrome (LES), present in 90% of non-immunocompromised patients with LES. However, there have been case reports which have shown its association between paraneoplastic syndrome affecting both central nervous system and the peripheral nervous system causing encephalomyelitis and sensory neuronopathy/neuropathy. We present a case of a young man, who presented with encephalomyelitis, and was further noted to have superimposed cervical polyradiculopathy associated with P/Q type VGCC antibodies...
November 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27445786/nitric-oxide-is-required-for-l-type-ca-2-channel-dependent-long-term-potentiation-in-the-hippocampus
#10
Beatrice M Pigott, John Garthwaite
Nitric oxide (NO) has long been implicated in the generation of long-term potentiation (LTP) and other types of synaptic plasticity, a role for which the intimate coupling between NMDA receptors (NMDARs) and the neuronal isoform of NO synthase (nNOS) is likely to be instrumental in many instances. While several types of synaptic plasticity depend on NMDARs, others do not, an example of which is LTP triggered by opening of L-type voltage-gated Ca(2+) channels (L-VGCCs) in postsynaptic neurons. In CA3-CA1 synapses in the hippocampus, NMDAR-dependent LTP (LTPNMDAR) appears to be primarily expressed postsynaptically whereas L-VGCC-dependent LTP (LTPL-VGCC), which often coexists with LTPNMDAR, appears mainly to reflect enhanced presynaptic transmitter release...
2016: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/27421665/an-expert-protocol-for-immunofluorescent-detection-of-calcium-channels-in-tsa-201-cells
#11
Peter Koch, Stefan Herzig, Jan Matthes
INTRODUCTION: Pore-forming subunits of voltage gated calcium channels (VGCC) are large membrane proteins (260kDa) containing 24 transmembrane domains. Despite transfection with viral promoter driven vectors, biochemical analysis of VGCC is often hampered by rather low expression levels in heterologous systems rendering VGCC challenging targets. Especially in immunofluorescent detection, calcium channels are demanding proteins. METHODS: We provide an expert step-by-step protocol with adapted conditions for handling procedures (tsA-201 cell culture, transient transfection, incubation time and temperature at 28°C or 37°C and immunostaining) to address the L-type calcium-channel pore Cav1...
July 12, 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27418672/calcium-channels-and-associated-receptors-in-malignant-brain-tumor-therapy
#12
Fernanda B Morrone, Marina P Gehring, Natália F Nicoletti
Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calcium-permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca(2+) activity plays an important role in the regulation of cell proliferation, and Ca(2+) signaling is altered in proliferating tumor cells...
September 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27405329/differential-regulation-of-human-paired-associative-stimulation-induced-and-theta-burst-stimulation-induced-plasticity-by-l-type-and-t-type-ca2-channels
#13
David Weise, Jakob Mann, Jost-Julian Rumpf, Stefan Hallermann, Joseph Classen
Activity-dependent changes of postsynaptic Ca(2+)-concentration are influenced by a variety of different Ca(2+)-channels and play an important role in synaptic plasticity. Paired associative stimulation (PAS) and theta-burst stimulation (TBS) are noninvasive magnetic stimulation protocols used in human subjects to induce lasting corticospinal excitability changes that have been likened to synaptic long-term potentiation and long-term depression. To better characterize the Ca(2+)-related physiological mechanisms underlying PAS- and TBS-induced plasticity, we examined the impact of different Ca(2+)-sources...
July 11, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27396568/store-operated-calcium-entry-is-required-for-sustained-contraction-and-ca-2-oscillations-of-airway-smooth-muscle
#14
Jun Chen, Michael J Sanderson
Asthma is characterized by airway hyper-responsiveness - the excessive contraction of airway smooth muscle. The extent of this airway contraction is proportional to the frequency of Ca(2+) oscillations within airway smooth muscle cells (ASMCs). Sustained Ca(2+) oscillations require a Ca(2+) influx to replenish Ca(2+) losses across the plasma membrane. Our previous studies implied store-operated calcium entry (SOCE) as the major pathway for this Ca(2+) influx. Here, we explore this hypothesis, by examining the effects of SOCE inhibitors (GSK7975A and GSK5498A) as well as L-type voltage-gated Ca(2+) channel (VGCC) inhibitors (nifedipine and nimodipine) on airway contraction and Ca(2+) oscillations and SOCE-mediated Ca(2+) influx in ASMCs within mouse precision-cut lung slices (PCLS)...
July 11, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27354560/protein-partners-of-the-calcium-channel-%C3%AE-subunit-highlight-new-cellular-functions
#15
REVIEW
Mohamad Rima, Marwa Daghsni, Ziad Fajloun, Ridha M'rad, Juan L Brusés, Michel Ronjat, Michel De Waard
Calcium plays a key role in cell signalling by its intervention in a wide range of physiological processes. Its entry into cells occurs mainly via voltage-gated calcium channels (VGCC), which are found not only in the plasma membrane of excitable cells but also in cells insensitive to electrical signals. VGCC are composed of different subunits, α1, β, α2δ and γ, among which the cytosolic β subunit (Cavβ) controls the trafficking of the channel to the plasma membrane, its regulation and its gating properties...
July 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27336942/antihypertensive-amlodipine-besilate-inhibits-growth-and-biofilm-of-human-fungal-pathogen-candida
#16
Payal Gupta, Reshmi Chanda, Nishant Rai, Vijay K Kataria, Navin Kumar
Candida albicans and Candida glabrata are two important human pathogens associated with high mortality. The anti-Candida potential of an antihypertensive drug, amlodipine besilate (AB), was studied against 10 strains of Candida, including 8 clinical isolates. AB is an inhibitor of voltage-gated Ca(2+) channel (VGCC) of mammals. CCH1 expresses in a part of Ca(2+) channel of Candida, which is a homologue of α subunit of mammalian VGCC. In plate assays, all strains of Candida showed sensitivity to AB on agar media at 256 μg/mL concentration, AB caused lethality at concentrations of 16 and 64 μg/mL in clinical isolates of C...
June 23, 2016: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27321892/dual-color-sted-microscopy-reveals-a-sandwich-structure-of-bassoon-and-piccolo-in-active-zones-of-adult-and-aged-mice
#17
Hiroshi Nishimune, Yomna Badawi, Shuuichi Mori, Kazuhiro Shigemoto
Presynaptic active zones play a pivotal role as synaptic vesicle release sites for synaptic transmission, but the molecular architecture of active zones in mammalian neuromuscular junctions (NMJs) at sub-diffraction limited resolution remains unknown. Bassoon and Piccolo are active zone specific cytosolic proteins essential for active zone assembly in NMJs, ribbon synapses, and brain synapses. These proteins are thought to colocalize and share some functions at active zones. Here, we report an unexpected finding of non-overlapping localization of these two proteins in mouse NMJs revealed using dual-color stimulated emission depletion (STED) super resolution microscopy...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27316997/identification-of-state-dependent-blockers-for-voltage-gated-calcium-channels-using-a-flipr-based-assay
#18
Alberto di Silvio, JeanFrancois Rolland, Michela Stucchi
The FLIPR (Fluorescent Imaging Plate Reader) system has been extensively used in the early stages of drug discovery for the identification of small molecules as a starting point for drug development, and for the pharmacological characterization of compounds. The main application of the system has been the measurement of intracellular Ca(2+) signals using fluorescent calcium indicators.This chapter describes the application of a protocol for the study and characterization of state-dependent blockers of Voltage-Gated Calcium Channels (VGCC) on the FLIPR(TETRA)...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27280380/gramine-derivatives-targeting-ca-2-channels-and-ser-thr-phosphatases-a-new-dual-strategy-for-the-treatment-of-neurodegenerative-diseases
#19
Rocío Lajarín-Cuesta, Carmen Nanclares, Juan-Alberto Arranz-Tagarro, Laura González-Lafuente, Raquel L Arribas, Monique Araujo de Brito, Luis Gandía, Cristóbal de Los Ríos
We describe the synthesis of gramine derivatives and their pharmacological evaluation as multipotent drugs for the treatment of Alzheimer's disease. An innovative multitarget approach is presented, targeting both voltage-gated Ca(2+) channels, classically studied for neurodegenerative diseases, and Ser/Thr phosphatases, which have been marginally aimed, even despite their key role in protein τ dephosphorylation. Twenty-five compounds were synthesized, and mostly their neuroprotective profile exceeded that offered by the head compound gramine...
July 14, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27270916/cav1-4-l-type-calcium-channels-contribute-to-calpain-activation-in-degenerating-photoreceptors-of-rd1-mice
#20
Christian Schön, François Paquet-Durand, Stylianos Michalakis
Retinitis pigmentosa is an inherited blinding disorder characterized by progressive degeneration and loss of photoreceptors. The exact mechanism of degeneration and cell death of photoreceptors is not known, but is thought to involve disturbed Ca2+-signaling. Ca2+ can enter the photoreceptor cell via outer segment cyclic nucleotide-gated (CNG) channels or synaptic Cav1.4 L-type voltage-gated calcium channels (VGCC). Previously, we have shown that genetic ablation of the Cngb1 gene encoding the B subunit of the rod CNG channel delays the fast progressing degeneration in the rd1 mutant mouse model of retinitis pigmentosa...
2016: PloS One
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