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https://www.readbyqxmd.com/read/28432032/neuronal-excitation-and-permeabilization-by-200-ns-pulsed-electric-field-an-optical-membrane-potential-study-with-fluovolt-dye
#1
Andrei G Pakhomov, Iurii Semenov, M Casciola, Shu Xiao
Electric field pulses of nano- and picosecond duration are a novel modality for neurostimulation, activation of Ca(2+) signaling, and tissue ablation. However it is not known how such brief pulses activate voltage-gated ion channels. We studied excitation and electroporation of hippocampal neurons by 200-ns pulsed electric field (nsPEF), by means of time-lapse imaging of the optical membrane potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more depolarized level, which was reached within <1ms...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28348377/bilirubin-augments-ca-2-load-of-developing-bushy-neurons-by-targeting-specific-subtype-of-voltage-gated-calcium-channels
#2
Min Liang, Xin-Lu Yin, Hai-Bo Shi, Chun-Yan Li, Xin-Yi Li, Ning-Ying Song, Hao-Song Shi, Yi Zhao, Lu-Yang Wang, Shan-Kai Yin
Neonatal brain is particularly vulnerable to pathological levels of bilirubin which elevates and overloads intracellular Ca(2+), leading to neurotoxicity. However, how voltage-gated calcium channels (VGCCs) are functionally involved in excess calcium influx remains unknown. By performing voltage-clamp recordings from bushy cells in the ventral cochlear nucleus (VCN) in postnatal rat pups (P4-17), we found the total calcium current density was more than doubled over P4-17, but the relative weight of VGCC subtypes changed dramatically, being relatively equal among T, L, N, P/Q and R-type at P4-6 to predominantly L, N, R over T and P/Q at P15-17...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28297674/nanoscale-structural-plasticity-of-the-active-zone-matrix-modulates-presynaptic-function
#3
Oleg O Glebov, Rachel E Jackson, Christian M Winterflood, Dylan M Owen, Ellen A Barker, Patrick Doherty, Helge Ewers, Juan Burrone
The active zone (AZ) matrix of presynaptic terminals coordinates the recruitment of voltage-gated calcium channels (VGCCs) and synaptic vesicles to orchestrate neurotransmitter release. However, the spatial organization of the AZ and how it controls vesicle fusion remain poorly understood. Here, we employ super-resolution microscopy and ratiometric imaging to visualize the AZ structure on the nanoscale, revealing segregation between the AZ matrix, VGCCs, and putative release sites. Long-term blockade of neuronal activity leads to reversible AZ matrix unclustering and presynaptic actin depolymerization, allowing for enrichment of AZ machinery...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28274920/h2o2-augments-cytosolic-calcium-in-nucleus-tractus-solitarii-neurons-via-multiple-voltage-gated-calcium-channels
#4
Tim D Ostrowski, Heather A Dantzler, Luis Polo-Parada, David D Kline
Reactive oxygen species (ROS) play a profound role in cardiorespiratory function under normal physiological conditions and disease states. ROS can influence neuronal activity by altering various ion channels and transporters. Within the nucleus tractus solitarii (nTS), a vital brainstem area for cardiorespiratory control, hydrogen peroxide (H2O2) induces sustained hyperexcitability following an initial depression of neuronal activity. The mechanism(s) associated with the delayed hyperexcitability are unknown...
March 8, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28265056/hysteresis-of-kcsa-potassium-channel-s-activation-deactivation-gating-is-caused-by-structural-changes-at-the-channel-s-selectivity-filter
#5
Cholpon Tilegenova, D Marien Cortes, Luis G Cuello
Mode-shift or hysteresis has been reported in ion channels. Voltage-shift for gating currents is well documented for voltage-gated cation channels (VGCC), and it is considered a voltage-sensing domain's (VSD) intrinsic property. However, uncoupling the Shaker K(+) channel's pore domain (PD) from the VSD prevented the mode-shift of the gating currents. Consequently, it was proposed that an open-state stabilization of the PD imposes a mechanical load on the VSD, which causes its mode-shift. Furthermore, the mode-shift displayed by hyperpolarization-gated cation channels is likely caused by structural changes at the channel's PD similar to those underlying C-type inactivation...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28235895/spike-and-neuropeptide-dependent-mechanisms-control-gnrh-neuron-nerve-terminal-ca-2-over-diverse-time-scales
#6
Karl J Iremonger, Robert Porteous, Allan E Herbison
Fast cell-to-cell communication in the brain is achieved by action potential-dependent synaptic release of neurotransmitters. The fast kinetics of transmitter release are determined by transient Ca(2+) elevations in presynaptic nerve terminals. Neuromodulators have previously been shown to regulate transmitter release by inhibiting presynaptic Ca(2+) influx. Few studies to date have demonstrated the opposite, that is, neuromodulators directly driving presynaptic Ca(2+) rises and increases in nerve terminal excitability...
February 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28212804/potassium-channels-in-regulation-of-vascular-smooth-muscle-contraction-and-growth
#7
W F Jackson
Potassium channels importantly contribute to the regulation of vascular smooth muscle (VSM) contraction and growth. They are the dominant ion conductance of the VSM cell membrane and importantly determine and regulate membrane potential. Membrane potential, in turn, regulates the open-state probability of voltage-gated Ca(2+) channels (VGCC), Ca(2+) influx through VGCC, intracellular Ca(2+), and VSM contraction. Membrane potential also affects release of Ca(2+) from internal stores and the Ca(2+) sensitivity of the contractile machinery such that K(+) channels participate in all aspects of regulation of VSM contraction...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28210211/app-as-a-protective-factor-in-acute-neuronal-insults
#8
REVIEW
Dimitri Hefter, Andreas Draguhn
Despite its key role in the molecular pathology of Alzheimer's disease (AD), the physiological function of amyloid precursor protein (APP) is unknown. Increasing evidence, however, points towards a neuroprotective role of this membrane protein in situations of metabolic stress. A key observation is the up-regulation of APP following acute (stroke, cardiac arrest) or chronic (cerebrovascular disease) hypoxic-ischemic conditions. While this mechanism may increase the risk or severity of AD, APP by itself or its soluble extracellular fragment APPsα can promote neuronal survival...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28202361/pre-clinical-evaluation-of-voltage-gated-calcium-channel-blockers-derived-from-the-spider-p-%C3%A2-nigriventer-in-glioma-progression
#9
Natália Fontana Nicoletti, Thaís Cristina Erig, Rafael Fernandes Zanin, Marcelo Ricardo Roxo, Nelson Pires Ferreira, Marcus Vinicius Gomez, Fernanda Bueno Morrone, Maria Martha Campos
This study investigated the effects of P/Q- and N-type voltage-gated calcium channel (VGCC) blockers derived from P. nigriventer in glioma progression, by means of in vitro and in vivo experiments. Glioma cells M059J, U-138MG and U-251MG were used to evaluate the antiproliferative effects of P/Q- and N-type VGCC inhibitors PhTx3-3 and Phα1β from P. nigriventer (0.3-100 pM), in comparison to MVIIC and MVIIA from C. magus (0.3-100 pM), respectively. The toxins were also analyzed in a glioma model induced by implantation of GL261 mouse cells...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28127114/cacna1b-cav2-2-overexpression-and-its-association-with-clinicopathologic-characteristics-and-unfavorable-prognosis-in-non-small-cell-lung-cancer
#10
Xiaoyu Zhou, Wei Wang, Shu Zhang, Xudong Wang, Zhiyuan Tang, Jun Gu, Jun Li, Jianan Huang
CACNA1B (Cav2.2) encodes an N-type voltage-gated calcium channel (VGCC) ubiquitously expressed in brain and peripheral nervous system that is important for regulating neuropathic pain. Because intracellular calcium concentration is a key player in cell proliferation and apoptosis, VGCCs are implicated in tumorigenesis. Recent studies have identified CACNA1B (Cav2.2) being overexpressed in prostate and breast cancer tissues when compared to adjacent normal tissues; however, its role in non-small cell lung cancer (NSCLC) has not been investigated...
2017: Disease Markers
https://www.readbyqxmd.com/read/28093211/pharmacological-properties-of-sak3-a-novel-t-type-voltage-gated-ca-2-channel-enhancer
#11
Yasushi Yabuki, Kazuya Matsuo, Hisanao Izumi, Hidaka Haga, Takashi Yoshida, Minoru Wakamori, Akikazu Kakei, Kenji Sakimura, Takaichi Fukuda, Kohji Fukunaga
T-type voltage-gated Ca(2+) channels (T-VGCCs) function in the pathophysiology of epilepsy, pain and sleep. However, their role in cognitive function remains unclear. We previously reported that the cognitive enhancer ST101, which stimulates T-VGCCs in rat cortical slices, was a potential Alzheimer's disease therapeutic. Here, we introduce a more potent T-VGCC enhancer, SAK3 (ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo [1,2-a]pyridin]-2-ene-3-carboxylate), and characterize its pharmacological properties in brain...
January 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27935186/coupling-of-a-voltage-gated-ca-2-channel-homologue-with-a-plasma-membrane-h-atpase-in-yeast
#12
Toshihiko Cho, Aya Ishii-Kato, Yuko Fukata, Yoshitaka Nakayama, Kazuko Iida, Masaki Fukata, Hidetoshi Iida
Yeast has a homologue of mammalian voltage-gated Ca(2+) channels (VGCCs), enabling the efficient uptake of Ca(2+) . It comprises two indispensable subunits, Cch1 and Mid1, equivalent to the mammalian pore-forming α1 and auxiliary α2 /δ subunits, respectively. Unlike the physiological roles of Cch1/Mid1 channels, the regulatory mechanisms of the yeast VGCC homologue remain unclear. Therefore, we screened candidate proteins that interact with Mid1 by an unbiased proteomic approach and identified a plasma membrane H(+) -ATPase, Pma1, as a candidate...
January 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/27872869/dynamic-association-of-calcium-channel-subunits-at-the-cellular-membrane
#13
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
#14
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
#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...
February 2017: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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