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Voltage Gated Calcium Channels

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https://www.readbyqxmd.com/read/29667130/beneficial-effects-of-the-calcium-channel-blocker-ctk-01512-2-in-a-mouse-model-of-multiple-sclerosis
#1
Rodrigo B M Silva, Samuel Greggio, Gianina T Venturin, Jaderson C da Costa, Marcus V Gomez, Maria M Campos
Voltage-gated calcium channels (VGCCs) play a critical role in neuroinflammatory diseases, such as multiple sclerosis (MS). CTK 01512-2 is a recombinant version of the peptide Phα1β derived from the spider Phoneutria nigriventer, which inhibits N-type VGCC/TRPA1-mediated calcium influx. We investigated the effects of this molecule in the mouse model of experimental autoimmune encephalomyelitis (EAE). The effects of CTK 01512-2 were compared to those displayed by ziconotide-a selective N-type VGCC blocker clinically used for chronic pain-and fingolimod-a drug employed for MS treatment...
April 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29655575/crmp2-neurofibromin-interface-drives-nf1-related-pain
#2
Aubin Moutal, Li Sun, Xiaofang Yang, Wennan Li, Song Cai, Shizhen Luo, Rajesh Khanna
An understudied symptom of the genetic disorder Neurofibromatosis type 1 (NF1) is chronic idiopathic pain. We used targeted editing of Nf1 in rats to provide direct evidence of a causal relationship between neurofibromin, the protein product of the Nf1 gene, and pain responses. Our study data identified a protein-interaction network with collapsin response meditator protein 2 (CRMP2) as a node and neurofibromin, syntaxin 1A, and the N-type voltage-gated calcium (CaV2.2) channel as interaction edges. Neurofibromin uncouples CRMP2 from syntaxin 1A...
April 12, 2018: Neuroscience
https://www.readbyqxmd.com/read/29655456/lambert-eaton-myasthenic-syndrome
#3
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
#4
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/29653257/%C3%AE-adrenergic-receptors-reduce-the-threshold-for-induction-and-stabilization-of-ltp-and-enhance-its-magnitude-via-multiple-mechanisms-in-the-ventral-but-not-the-dorsal-hippocampus
#5
Vassilios Papaleonidopoulos, Costas Papatheodoropoulos
The hippocampus is a functionally heterogeneous structure with the cognitive and emotional signal processing ascribed to the dorsal (DH) and the ventral hippocampus (VH) respectively. However, the underlying mechanisms are poorly understood. Noradrenaline is released in hippocampus during emotional arousal modulating synaptic plasticity and memory consolidation through activation of β adrenergic receptors (β-ARs). Using recordings of field excitatory postsynaptic potentials from the CA1 field of adult rat hippocampal slices we demonstrate that long-term potentiation (LTP) induced either by theta-burst stimulation (TBS) that mimics a physiological firing pattern of hippocampal neurons or by high-frequency stimulation is remarkably more sensitive to β-AR activation in VH than in DH...
April 10, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29621262/rescue-of-hyperexcitability-in-hippocampal-ca1-neurons-from-mecp2-y-mouse-through-surface-potential-neutralization
#6
Saju Balakrishnan, Sergej L Mironov
Hyperventilation is a known feature of Rett syndrome (RTT). However, how hyperventilation is related to other RTT symptoms such as hyperexcitability is unknown. Intense breathing during hyperventilation induces hypocapnia and culminates in respiratory alkalosis. Alkalinization of extracellular milieu can trigger epilepsy in patients who already have neuronal hyperexcitability. By combining patch-clamp electrophysiology and quantitative glutamate imaging, we compared excitability of CA1 neurons of WT and Mecp2 (-/y) mice, and analyzed the biophysical properties of subthreshold membrane channels...
2018: PloS One
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
#7
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
#8
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/29589117/the-degenerin-region-of-the-human-bile-acid-sensitive-ion-channel-basic-is-involved-in-channel-inhibition-by-calcium-and-activation-by-bile-acids
#9
Alexandr V Ilyaskin, Sonja A Kirsch, Rainer A Böckmann, Heinrich Sticht, Christoph Korbmacher, Silke Haerteis, Alexei Diakov
The bile acid-sensitive ion channel (BASIC) is a member of the ENaC/degenerin family of ion channels. It is activated by bile acids and inhibited by extracellular Ca2+ . The aim of this study was to explore the molecular mechanisms mediating these effects. The modulation of BASIC function by extracellular Ca2+ and tauro-deoxycholic acid (t-DCA) was studied in Xenopus laevis oocytes heterologously expressing human BASIC using the two-electrode voltage-clamp and outside-out patch-clamp techniques. Substitution of aspartate D444 to alanine or cysteine in the degenerin region of BASIC, a region known to be critically involved in channel gating, resulted in a substantial reduction of BASIC Ca2+ sensitivity...
March 27, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29580153/peripheral-nerve-injury-increases-contribution-of-l-type-calcium-channels-to-synaptic-transmission-in-spinal-lamina-ii-role-of-%C3%AE-2%C3%AE-1-subunits
#10
Sascha Ra Alles, Esperanza Garcia, Sridhar Balasubramanyan, Karen Jones, John R Tyson, Twinkle Joy, Terrance P Snutch, Peter A Smith
Background Following peripheral nerve chronic constriction injury, the accumulation of the α2δ-1 auxiliary subunit of voltage-gated Ca2+ channels in primary afferent terminals contributes to the onset of neuropathic pain. Overexpression of α2δ-1 in Xenopus oocytes increases the opening properties of Cav 1.2 L-type channels and allows Ca2+ influx at physiological membrane potentials. We therefore posited that L-type channels play a role in neurotransmitter release in the superficial dorsal horn in the chronic constriction injury model of neuropathic pain...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29578032/ca-v-3-1-isoform-of-t-type-calcium-channels-supports-excitability-of-rat-and-mouse-ventral-tegmental-area-neurons
#11
Matthew E Tracy, Vesna Tesic, Tamara Timic Stamenic, Srdjan M Joksimovic, Nicolas Busquet, Vesna Jevtovic-Todorovic, Slobodan M Todorovic
Recent data have implicated voltage-gated calcium channels in the regulation of the excitability of neurons within the mesolimbic reward system. While the attention of most research has centered on high voltage L-type calcium channel activity, the presence and role of the low voltage-gated T-type calcium channel (T-channels) has not been well explored. Hence, we investigated T-channel properties in the neurons of the ventral tegmental area (VTA) utilizing wild-type (WT) rats and mice, CaV 3.1 knock-out (KO) mice, and TH-eGFP knock-in (KI) rats in acute horizontal brain slices of adolescent animals...
March 22, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29573716/wi-fi-is-an-important-threat-to-human-health
#12
Martin L Pall
Repeated Wi-Fi studies show that Wi-Fi causes oxidative stress, sperm/testicular damage, neuropsychiatric effects including EEG changes, apoptosis, cellular DNA damage, endocrine changes, and calcium overload. Each of these effects are also caused by exposures to other microwave frequency EMFs, with each such effect being documented in from 10 to 16 reviews. Therefore, each of these seven EMF effects are established effects of Wi-Fi and of other microwave frequency EMFs. Each of these seven is also produced by downstream effects of the main action of such EMFs, voltage-gated calcium channel (VGCC) activation...
March 21, 2018: Environmental Research
https://www.readbyqxmd.com/read/29572644/expression-of-a-constitutively-active-human-insulin-receptor-in-hippocampal-neurons-does-not-alter-vgcc-currents
#13
H N Frazier, K L Anderson, S Maimaiti, A O Ghoweri, S D Kraner, G J Popa, K K Hampton, M D Mendenhall, C M Norris, R J Craven, O Thibault
Memory and cognitive decline are the product of numerous physiological changes within the aging brain. Multiple theories have focused on the oxidative, calcium, cholinergic, vascular, and inflammation hypotheses of brain aging, with recent evidence suggesting that reductions in insulin signaling may also contribute. Specifically, a reduction in insulin receptor density and mRNA levels has been implicated, however, overcoming these changes remains a challenge. While increasing insulin receptor occupation has been successful in offsetting cognitive decline, alternative molecular approaches should be considered as they could bypass the need for brain insulin delivery...
March 23, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29569306/optogenetic-control-of-voltage-gated-calcium-channels
#14
Yubin Zhou, Guolin Ma, Jindou Liu, Yuepeng Ke, Xin Liu, Minyong Li, Fen Wang, Gang Han, Yun Huang, Youjun Wang
Voltage-gated Ca2+ (CaV) channels mediate Ca2+ entry into excitable cells to regulate a myriad of cellular events following membrane depolarization. Here, we report the engineering of RGK GTPases, a class of genetically encoded CaV channel modulators, to enable photo-tunable modulation of CaV channel activity in excitable mammalian cells. This optogenetic toolkit (designated optoRGK) tailored for CaV channels will find broad applications in interrogating a wide range of CaV-mediated physiological processes in multiple systems...
March 23, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29568937/genetic-analysis-of-sick-sinus-syndrome-in-a-family-harboring-compound-cacna1c-and-ttn-mutations
#15
Yao-Bin Zhu, Jie-Wei Luo, Fen Jiang, Gui Liu
Sick sinus syndrome (SSS) is a sinus node dysfunction characterized by severe sinus bradycardia. SSS results in insufficient blood supply to the brain, heart, kidneys, and other organs and is associated with the increased risk of sudden cardiac death. Bradyarrhythmia appears in the absence of any associated cardiac pathology and displays a genetic legacy. The present study identified a family with primary manifestation of sinus bradycardia (five individuals) along with early repolarization (four individuals) and atrial fibrillation (one individual)...
March 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29567962/cryo-em-structure-of-the-polycystic-kidney-disease-like-channel-pkd2l1
#16
Qiang Su, Feizhuo Hu, Yuxia Liu, Xiaofei Ge, Changlin Mei, Shengqiang Yu, Aiwen Shen, Qiang Zhou, Chuangye Yan, Jianlin Lei, Yanqing Zhang, Xiaodong Liu, Tingliang Wang
PKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is involved in the sour sensation and other pH-dependent processes. PKD2L1 is believed to be a nonselective cation channel that can be regulated by voltage, protons, and calcium. Despite its considerable importance, the molecular mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine the PKD2L1 atomic structure at 3.38 Å resolution by cryo-electron microscopy, whereby side chains of nearly all residues are assigned...
March 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29564789/analysis-of-feedback-signaling-from-horizontal-cells-to-photoreceptors-in-mice
#17
Arlene A Hirano, Xue Liu, Nicholas C Brecha, Steven Barnes
Genetic manipulation of horizontal cells using a Connexin57-iCre mouse (Cx57-iCre) line combined with calcium imaging is proving to be a valuable method to study horizontal cell feedback inhibition onto photoreceptor terminals. While it is accepted that horizontal cells provide lateral inhibitory feedback to photoreceptors, the cellular mechanisms that underlie this feedback inhibition remain only partially elucidated. Feedback inhibition of photoreceptors acts via modulation of their voltage-gated calcium channels at their synaptic terminal...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29563324/binding-characteristics-and-analgesic-effects-of-mirogabalin-a-novel-ligand-for-the-%C3%AE-2-%C3%AE-subunit-of-voltage-gated-calcium-channels
#18
Yuki Domon, Naohisa Arakawa, Tatsuya Inoue, Fumihiko Matsuda, Makoto Takahashi, Naotoshi Yamamura, Kiyonori Kai, Yutaka Kitano
Mirogabalin ([(1 R ,5 S ,6 S )-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid), a novel ligand for the α2 δ subunit of voltage-gated calcium channels, is being developed to treat pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. In the present study, we investigated the in vitro binding characteristics and in vivo analgesic effects of mirogabalin, compared to those of pregabalin, a standard α2 δ ligand. Mirogabalin showed potent and selective binding affinities for the α2 δ subunits, while having no effects on 186 off-target proteins...
March 21, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29556214/calcium-channels-in-postnatal-development-of-rat-pancreatic-beta-cells-and-their-role-in-insulin-secretion
#19
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
https://www.readbyqxmd.com/read/29545968/calcium-channel-%C3%AE-2%C3%AE-1-subunit-as-a-novel-biomarker-for-diagnosis-of-hepatocellular-carcinoma
#20
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
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