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P/q type calcium channels

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https://www.readbyqxmd.com/read/29655456/lambert-eaton-myasthenic-syndrome
#1
REVIEW
Vita G Kesner, Shin J Oh, Mazen M Dimachkie, Richard J Barohn
Lambert-Eaton myasthenic syndrome is a paraneoplastic or primary autoimmune neuromuscular junction disorder characterized by proximal weakness, autonomic dysfunction and ariflexia. The characteristic symptoms are thought to be caused by antibodies generated against the P/Q-type voltage-gated calcium channels present on presynaptic nerve terminals and by diminished release of acetylcholine. More than half of Lambert-Eaton myasthenic syndrome cases are associated with small cell lung carcinoma. Diagnosis is confirmed by serologic testing and electrophysiologic studies...
May 2018: Neurologic Clinics
https://www.readbyqxmd.com/read/29655446/practical-anatomy-of-the-neuromuscular-junction-in-health-and-disease
#2
REVIEW
Hiroshi Nishimune, Kazuhiro Shigemoto
Neuromuscular junctions (NMJs) form between nerve terminals of spinal cord motor neurons and skeletal muscles, and perisynaptic Schwann cells and kranocytes cap NMJs. One muscle fiber has one NMJ, which is innervated by one motor nerve terminal. NMJs are excitatory synapses that use P/Q-type voltage-gated calcium channels to release the neurotransmitter acetylcholine. Acetylcholine receptors accumulate at the postsynaptic specialization called the end plate on the muscle fiber membrane, the sarcolemma. Proteins essential for the organization of end plates include agrin secreted from nerve terminals, Lrp4 and MuSK receptors for agrin, and Dok-7 and rapsyn cytosolic proteins in the muscle...
May 2018: Neurologic Clinics
https://www.readbyqxmd.com/read/29608168/combining-optogenetics-with-artificial-micrornas-to-characterize-the-effects-of-gene-knockdown-on-presynaptic-function-within-intact-neuronal-circuits
#3
Agnes Thalhammer, Fanny Jaudon, Lorenzo A Cingolani
The purpose of this protocol is to characterize the effect of gene knockdown on presynaptic function within intact neuronal circuits. We describe a workflow on how to combine artificial microRNA (miR)-mediated RNA interference with optogenetics to achieve selective stimulation of manipulated presynaptic boutons in acute brain slices. The experimental approach involves the use of a single viral construct and a single neuron-specific promoter to drive the expression of both an optogenetic probe and artificial miR(s) against presynaptic gene(s)...
March 14, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29603093/oxaliplatin-modulates-the-characteristics-of-voltage-gated-calcium-channels-and-action-potentials-in-small-dorsal-root-ganglion-neurons-of-rats
#4
Linda-Isabell Schmitt, Markus Leo, Christoph Kleinschnitz, Tim Hagenacker
Oxaliplatin is important for treating colorectal cancer. Although oxaliplatin is highly effective, it has severe side effects, of which neurotoxicity in dorsal root ganglion (DRG) neurons is one of the most common. The key mechanisms of this neurotoxicity are still controversial. However, disturbances of calcium homeostasis in DRG neurons have been suggested to mediate oxaliplatin neurotoxicity. By using whole-cell patch-clamp and current-clamp techniques, as well as immunocytochemical staining, we examined the influence of short- and long-term exposure to oxaliplatin on voltage-gated calcium channels (VGCC) and different VGCC subtypes in small DRG neurons of rats in vitro...
March 30, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29562421/-downregulation-of-large-conductance-calcium-activated-potassium-channels-in-paraventricular-nucleus-contributes-to-sympathoexcitation-in-rats-with-chronic-heart-failure
#5
R J Wang, M L Wen, Q Zhou, X W Wei, H Li, Y B Zhao, Y F Qi, J Luan, X F Zhou
Objective: To elucidate the association between large conductance calcium-activated potassium channels (BKCa ) in the paraventricular hypothalamic nucleus (PVN) and sympathetic outflow in rats with chronic heart failure (CHF) . Methods: Male Wistar rats (6-7 weeks old) were randomized to sham operated group and CHF group (coronary artery ligation) . Two weeks after operation, BKCa inhibitor Iberiotoxin (IBTX) was infused into PVN by osmotic minipumps, rats were divided into following groups: sham+aCSF, CHF+aCSF, sham+low dose IBTX (0...
March 24, 2018: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29482112/role-of-voltage-gated-calcium-channels-on-striatal-dopamine-release-induced-by-inorganic-mercury-in-freely-moving-rats
#6
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
https://www.readbyqxmd.com/read/29427102/spinocerebellum-ataxia-type-6-molecular-mechanisms-and-calcium-channel-genetics
#7
Xiaofei Du, Christopher Manuel Gomez
Spinocerebellar ataxia (SCA) type 6 is an autosomal dominant disease affecting cerebellar degeneration. Clinically, it is characterized by pure cerebellar dysfunction, slowly progressive unsteadiness of gait and stance, slurred speech, and abnormal eye movements with late onset. Pathological findings of SCA6 include a diffuse loss of Purkinje cells, predominantly in the cerebellar vermis. Genetically, SCA6 is caused by expansion of a trinucleotide CAG repeat in the last exon of longest isoform CACNA1A gene on chromosome 19p13...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29392225/effect-of-the-spider-toxin-tx3-3-on-spinal-processing-of-sensory-information-in-naive-and-neuropathic-rats-an-in-vivo-electrophysiological-study
#8
Gerusa D Dalmolin, Kirsty Bannister, Leonor Gonçalves, Shafaq Sikandar, Ryan Patel, Marta do Nascimento Cordeiro, Marcus Vinícius Gomez, Juliano Ferreira, Anthony H Dickenson
Introduction: Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. Objectives: In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL)...
July 2017: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/29366381/an-atypical-rett-syndrome-phenotype-due-to-a-novel-missense-mutation-in-cacna1a
#9
Madison V Epperson, Michael E Haws, Shannon M Standridge, Donald L Gilbert
BACKGROUND: Some typical and atypical Rett syndrome patients lack known genetic mutations. Mutations in the P/Q type calcium channel CACNA1A have been implicated in epileptic encephalopathy, familial hemiplegic migraine, episodic ataxia 2, and spinocerebellar ataxia 6, but not Rett syndrome. Patient Description: The authors describe a female patient with developmental regression and a de novo, likely pathogenic mutation in CACNA1A who meets 3 of 4 main criteria (stereotypic hand movements, loss of purposeful hand movements, gait disturbance), and 6 of 11 supportive criteria (impaired sleep, abnormal tone, vasomotor disturbance, scoliosis, growth retardation, and screaming spells) for atypical Rett syndrome...
January 1, 2018: Journal of Child Neurology
https://www.readbyqxmd.com/read/29189554/paraneoplastic-lambert-eaton-myasthenic-syndrome-with-limbic-encephalitis-clinical-correlation-with-the-coexistence-of-anti-vgcc-and-anti-gabab-receptor-antibodies
#10
Jonathan J Cho, James P Wymer
OBJECTIVE: To characterize Lambert-Eaton myasthenic syndrome and limbic encephalitis with coexistent voltage-gated calcium channel (VGCC) antibody and γ-aminobutyric acid (GABA) B receptor antibody. METHODS: Case study. RESULTS: A 57-year-old man presented with 6 months of weakness, unsteadiness, and vision difficulties. Examination revealed proximal weakness and diminished reflexes. Electrodiagnostic study revealed low-amplitude motor potentials and facilitation on high-frequency stimulation...
December 2017: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/29166599/maturation-of-cerebellar-purkinje-cell-population-activity-during-postnatal-refinement-of-climbing-fiber-network
#11
Jean-Marc Good, Michael Mahoney, Taisuke Miyazaki, Kenji F Tanaka, Kenji Sakimura, Masahiko Watanabe, Kazuo Kitamura, Masanobu Kano
Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF) to Purkinje cell (PC) network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29093415/a-case-of-paraneoplastic-cerebellar-degeneration-and-lambert-eaton-myasthenic-syndrome-associated-with-neuroendocrine-carcinoma-of-the-oropharynx
#12
Junji Takasugi, Munehisa Shimamura, Toru Koda, Toshihiro Kishikawa, Atsushi Hanamoto, Hidenori Inohara, Kazuaki Sato, Eiichi Morii, Masakatsu Motomura, Manabu Sakaguchi, Yuji Nakatsuji, Hideki Mochizuki
Paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome (PCD-LEMS) are usually associated with small-cell lung carcinoma (SCLC). PCD-LEMS with extrapulmonary non-SCLC tumors; however, has not been previously reported. A 78-year-old man presented with dysarthria, dysphagia, staggering gait, and lower extremity muscle fatigue. He was diagnosed with PCD-LEMS associated with neuroendocrine carcinoma of the oropharynx, based on the histological findings of the biopsy, the existence of antibodies against P/Q-type voltage-gated calcium channels, and an incremental response of the compound muscle action potentials during repetitive nerve stimulation tests...
November 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29033792/spontaneous-and-evoked-activity-from-murine-ventral-horn-cultures-on-microelectrode-arrays
#13
Bryan J Black, Rahul Atmaramani, Joseph J Pancrazio
Motor neurons are the site of action for several neurological disorders and paralytic toxins, with cell bodies located in the ventral horn (VH) of the spinal cord along with interneurons and support cells. Microelectrode arrays (MEAs) have emerged as a high content assay platform for mechanistic studies and drug discovery. Here, we explored the spontaneous and evoked electrical activity of VH cultures derived from embryonic mouse spinal cord on multi-well plates of MEAs. Primary VH cultures from embryonic day 15-16 mice were characterized by expression of choline acetyltransferase (ChAT) by immunocytochemistry...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28990373/sigma-1-receptor-agonist-increases-axon-outgrowth-of-hippocampal-neurons-via-voltage-gated-calcium-ions-channels
#14
Dong Li, Shu-Zhuo Zhang, Yu-Hong Yao, Yun Xiang, Xiao-Yun Ma, Xiao-Li Wei, Hai-Tao Yan, Xiao-Yan Liu
INTRODUCTION: Sigma-1 receptors (Sig-1Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig-1R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig-1R-mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig-1R on axon outgrowth are not fully understood. METHODS: To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured naïve hippocampal neurons before and after the application of the Sig-1R agonist, SA4503...
October 8, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28930822/five-years-experience-on-3-4-diaminopyridine-phosphate-in-lambert-eaton-syndrome-case-reports
#15
Simona Portaro, Teresa Brizzi, Stefano Sinicropi, Alberto Cacciola, Maria Cristina De Cola, Alessia Bramanti, Demetrio Milardi, Antonino Lupica, Placido Bramanti, Antonio Toscano, Carmelo Rodolico
RATIONALE: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert-Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. PATIENT CONCERNS: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28901011/persistent-aberrant-cortical-phase-amplitude-coupling-following-seizure-treatment-in-absence-epilepsy-models
#16
Atul Maheshwari, Abraham Akbar, Mai Wang, Rachel L Marks, Katherine Yu, Suhyeorn Park, Brett L Foster, Jeffrey L Noebels
KEY POINTS: In two monogenic models of absence epilepsy, interictal beta/gamma power is augmented in homozygous stargazer (stg/stg) but not homozygous tottering (tg/tg) mice. There are distinct gene-linked patterns of aberrant phase-amplitude coupling in the interictal EEG of both stg/stg and tg/tg mice, compared to +/+ and stg/+ mice. Treatment with ethosuximide significantly blocks seizures in both genotypes, but the abnormal phase-amplitude coupling remains. Seizure-free stg/+ mice have normal power and phase-amplitude coupling, but beta/gamma power is significantly reduced with NMDA receptor blockade, revealing a latent cortical network phenotype that is separable from, and therefore not a result of, seizures...
December 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28882644/postsynaptic-n-type-or-p-q-type-calcium-channels-mediate-long-term-potentiation-by-group-i-metabotropic-glutamate-receptors-in-the-trigeminal-oralis
#17
Haein Weon, Tae Wan Kim, Dong-Ho Youn
AIMS: Both N-type and P/Q-type voltage-gated Ca(2+) channels (VGCCs) are involved in the induction of long-term potentiation (LTP), the long-lasting increase of synaptic strength, in the central nervous system. To provide further information on the roles of N-type and P/Q-type VGCCs in the induction of LTP at excitatory synapses of trigeminal primary afferents in the spinal trigeminal subnucleus oralis (Vo), we investigated whether they contribute to the induction of LTP by activation of group I metabotropic glutamate receptors (mGluRs)...
November 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28866764/l-type-calcium-channels-in-exocytosis-and-endocytosis-of-chromaffin-cells
#18
REVIEW
Carmen Nanclares, Andrés M Baraibar, Luis Gandía
The coexistence of different subtypes of voltage-dependent calcium channels (VDCC) within the same chromaffin cell (CC) and the marked interspecies variability in the proportion of VDCC subtypes that are present in the plasmalemma of the CCs raises the question on their roles in controlling different physiological functions. Particularly relevant seems to be the role of VDCCs in the regulation of the exocytotic neurotransmitter release process, and its tightly coupled membrane retrieval (endocytosis) process since both are Ca2+ -dependent processes...
January 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28734867/p-q-type-voltage-gated-calcium-channels-mediate-the-ethanol-and-crf-sensitivity-of-central-amygdala-gabaergic-synapses
#19
F P Varodayan, M L Logrip, M Roberto
The central amygdala (CeA) GABAergic system is hypothesized to drive the development of alcohol dependence, due to its pivotal roles in the reinforcing actions of alcohol and the expression of negative emotion, anxiety and stress. Recent work has also identified an important role for the CeA corticotropin-releasing factor (CRF) system in the interaction between anxiety/stress and alcohol dependence. We have previously shown that acute alcohol and CRF each increase action potential-independent GABA release in the CeA via their actions at presynaptic CRF type 1 receptors (CRF1s); however, the shared mechanism employed by these two compounds requires further investigation...
July 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28733833/neuroanatomy-of-pain-deficiency-and-cross-modal-activation-in-calcium-channel-subunit-cacn-%C3%AE-2%C3%AE-3-knockout-mice
#20
Julia Landmann, Franziska Richter, Ana-Maria Oros-Peusquens, N Jon Shah, Joseph Classen, G Gregory Neely, Angelika Richter, Josef M Penninger, Ingo Bechmann
The phenotype of calcium channel subunit (CACN) α2δ3 knockout (KO) mice includes sensory cross-activation and deficient pain perception. Sensory cross-activation defines the activation of a sensory cortical region by input from another modality due to reorganization in the brain such as after sensory loss. To obtain mechanistic insight into both phenomena, we employed a comprehensive battery of neuroanatomical techniques. While CACNα2δ3 was ubiquitously expressed in wild-type mice, it was absent in α2δ3 KO animals...
July 21, 2017: Brain Structure & Function
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