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Voltage-dependent calcium channels

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https://www.readbyqxmd.com/read/29773754/a-critical-neurodevelopmental-role-for-l-type-voltage-gated-calcium-channels-in-neurite-extension-and-radial-migration
#1
Satoshi Kamijo, Yuichiro Ishii, Shin-Ichiro Horigane, Kanzo Suzuki, Masamichi Ohkura, Junichi Nakai, Hajime Fujii, Sayaka Takemoto-Kimura, Haruhiko Bito
In spite of many association studies linking gene polymorphisms and mutations of L-type Voltage-Gated Ca2+ Channels (VGCC) in neurodevelopmental disorders, such as autism and schizophrenia, specific L-type VGCC roles during brain development remain unclear. Yet, calcium signaling has been shown to be essential for neurodevelopmental processes such as sculpting of neurites, functional wiring and fine tuning of growing networks. To bridge this gap, we performed submembraneous calcium imaging using a membrane-tethered genetically-encoded calcium indicator (GECI) Lck-G-CaMP7...
May 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29755321/voltage-gated-calcium-channel-activation-by-backpropagating-action-potentials-downregulates-nmdar-function
#2
Anne-Kathrin Theis, Balázs Rózsa, Gergely Katona, Dietmar Schmitz, Friedrich W Johenning
The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs) propagate back into the dendritic tree and activate voltage gated Ca2+ channels (VGCCs). For spines, this global mode of spine Ca2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs) result in long-term enhancement of spine VGCCs...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29748133/retinoic-acid-inhibits-neuronal-voltage-gated-calcium-channels
#3
Eric de Hoog, Mark K Lukewich, Gaynor E Spencer
Retinoic acid is the active metabolite of vitamin A and regulates several important cellular processes by activating retinoic acid receptors (RAR) and retinoid X receptors (RXR). These receptors generally act as transcription factors, though non-genomic actions of both retinoic acid and the receptors have also been reported. One such nongenomic effect includes the modulation of Ca2+ levels during homeostatic synaptic plasticity in the hippocampus. Retinoic acid can thus affect Ca2+ signaling and can potentially control both synaptic plasticity and neuronal firing...
February 13, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29746088/structure-activity-studies-reveal-the-molecular-basis-for-gabab-receptor-mediated-inhibition-of-high-voltage-activated-calcium-channels-by-%C3%AE-conotoxin-vc1-1
#4
Mahsa Sadeghi, Bodil B Carstens, Brid P Callaghan, James T Daniel, Han Shen Tae, Tracey O'Donnell, Joel Castro, Stuart M Brierley, David J Adams, David J Craik, Richard J Clark
α-Conotoxins are disulfide-bonded peptides from cone snail venoms and are characterized by their affinity for nicotinic acetylcholine receptors (nAChR). Several α-conotoxins with distinct selectivity for nAChR subtypes have been identified as potent analgesics in animal models of chronic pain. However, a number of α-conotoxins have been shown to inhibit N-type calcium channel currents in rodent dissociated dorsal root ganglion (DRG) neurons via activation of G protein-coupled GABAB receptors (GABABR). Therefore it is unclear whether activation of GABABR or inhibition of α9α10 nAChRs is the analgesic mechanism...
May 10, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29743299/the-akap-cypher-zasp-contributes-to-%C3%AE-adrenergic-pka-stimulation-of-cardiac-ca-v-1-2-calcium-channels
#5
Haijie Yu, Can Yuan, Ruth E Westenbroek, William A Catterall
Stimulation of the L-type Ca2+ current conducted by CaV 1.2 channels in cardiac myocytes by the β-adrenergic/protein kinase A (PKA) signaling pathway requires anchoring of PKA to the CaV 1.2 channel by an A-kinase anchoring protein (AKAP). However, the AKAP(s) responsible for regulation in vivo remain unknown. Here, we test the role of the AKAP Cypher/Zasp in β-adrenergic regulation of CaV 1.2 channels using physiological studies of cardiac ventricular myocytes from young-adult mice lacking the long form of Cypher/Zasp (LCyphKO mice)...
May 9, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29742403/alternative-splicing-at-n-terminus-and-domain-i-modulates-ca-v-1-2-inactivation-and-surface-expression
#6
Peter Bartels, Dejie Yu, Hua Huang, Zhenyu Hu, Stefan Herzig, Tuck Wah Soong
The CaV 1.2 L-type calcium channel is a key conduit for Ca2+ influx to initiate excitation-contraction coupling for contraction of the heart and vasoconstriction of the arteries and for altering membrane excitability in neurons. Its α1C pore-forming subunit is known to undergo extensive alternative splicing to produce many CaV 1.2 isoforms that differ in their electrophysiological and pharmacological properties. Here, we examined the structure-function relationship of human CaV 1.2 with respect to the inclusion or exclusion of mutually exclusive exons of the N-terminus exons 1/1a and IS6 segment exons 8/8a...
May 8, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29738885/regulation-of-seizure-induced-mecp2-ser421-phosphorylation-in-the-developing-brain
#7
Evan C Rosenberg, Jocelyn J Lippman-Bell, Marcus Handy, Samantha S Soldan, Sanjay Rakhade, Cristina Hilario-Gomez, Kaitlyn Folweiler, Leah Jacobs, Frances E Jensen
Neonatal seizures disrupt normal synaptic maturation and often lead to later-life epilepsy and cognitive deficits. During early life, the brain exhibits heightened synaptic plasticity, in part due to a developmental overabundance of CaV 1.2 L-type voltage gated calcium (Ca2+ ) channels (LT-VGCCs) and Ca2+ -permeable AMPARs (CP-AMPARs) lacking GluA2 subunits. We hypothesized that early-life seizures overactivate these channels, in turn dysregulating Ca2+ -dependent signaling pathways including that of methyl-CPG-binding protein 2 (MeCP2), a transcription factor implicated in the autism spectrum disorder (ASD) Rett Syndrome...
May 5, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29733866/interactive-effects-of-early-life-stress-and-cacna1c-genotype-on-cortisol-awakening-response
#8
K Klaus, K Butler, H Gutierrez, S J Durrant, K Pennington
The rs1006737 (A/G) single nucleotide polymorphism within the gene encoding the Cav 1.2 subunit of the L-type voltage-dependent calcium channel (CACNA1C) has been strongly implicated in psychiatric disorders. In addition, calcium channels are sensitive to the effects of glucocorticoids and functional variation may contribute to altered stress responsivity. This study aimed to investigate the role of early life stress (ELS) and its interaction with CACNA1C rs1006737 in affecting the cortisol awakening response (CAR), an indicator of HPA-axis function...
May 4, 2018: Biological Psychology
https://www.readbyqxmd.com/read/29733375/tissue-selective-restriction-of-rna-editing-of-cav1-3-by-splicing-factor-srsf9
#9
Hua Huang, Katannya Kapeli, Wenhao Jin, Yuk Peng Wong, Thiruma Valavan Arumugam, Joanne Huifen Koh, Sumitra Srimasorn, Karthik Mallilankaraman, John Jia En Chua, Gene W Yeo, Tuck Wah Soong
Adenosine DeAminases acting on RNA (ADAR) catalyzes adenosine-to-inosine (A-to-I) conversion within RNA duplex structures. While A-to-I editing is often dynamically regulated in a spatial-temporal manner, the mechanisms underlying its tissue-selective restriction remain elusive. We have previously reported that transcripts of voltage-gated calcium channel CaV1.3 are subject to brain-selective A-to-I RNA editing by ADAR2. Here, we show that editing of CaV1.3 mRNA is dependent on a 40 bp RNA duplex formed between exon 41 and an evolutionarily conserved editing site complementary sequence (ECS) located within the preceding intron...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29728980/backbone-resonance-assignments-of-complexes-of-apo-human-calmodulin-bound-to-iq-motif-peptides-of-voltage-dependent-sodium-channels-na-v-1-1-na-v-1-4-and-na-v-1-7
#10
Holly M Isbell, Adina M Kilpatrick, Zesen Lin, Ryan Mahling, Madeline A Shea
Human voltage-gated sodium (NaV ) channels are critical for initiating and propagating action potentials in excitable cells. Nine isoforms have different roles but similar topologies, with a pore-forming α-subunit and auxiliary transmembrane β-subunits. NaV pathologies lead to debilitating conditions including epilepsy, chronic pain, cardiac arrhythmias, and skeletal muscle paralysis. The ubiquitous calcium sensor calmodulin (CaM) binds to an IQ motif in the C-terminal tail of the α-subunit of all NaV isoforms, and contributes to calcium-dependent pore-gating in some channels...
May 4, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29721607/hydrogen-sulphide-facilitates-exocytosis-by-regulating-the-handling-of-intracellular-calcium-by-chromaffin-cells
#11
Ricardo de Pascual, Andrés M Baraibar, Iago Méndez-López, Martín Pérez-Ciria, Ignacio Polo-Vaquero, Luis Gandía, Sunny E Ohia, Antonio G García, Antonio M G de Diego
Gasotransmitter hydrogen sulphide (H2 S) has emerged as a regulator of multiple physiological and pathophysiological processes throughout. Here, we have investigated the effects of NaHS (fast donor of H2 S) and GYY4137 (GYY, slow donor of H2 S) on the exocytotic release of catecholamines from fast-perifused bovine adrenal chromaffin cells (BCCs) challenged with sequential intermittent pulses of a K+ -depolarizing solution. Both donors caused a concentration-dependent facilitation of secretion. This was not due to an augmentation of Ca2+ entry through voltage-activated Ca2+ channels (VACCs) because, in fact, NaHS and GYY caused a mild inhibition of whole-cell Ca2+ currents...
May 2, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29720608/drosophila-voltage-gated-calcium-channel-%C3%AE-1-subunits-regulate-cardiac-function-in-the-aging-heart
#12
Alexander Lam, Priyanka Karekar, Kajol Shah, Girija Hariharan, Michelle Fleyshman, Harmehak Kaur, Harpreet Singh, Shubha Gururaja Rao
Ion channels maintain numerous physiological functions and regulate signaling pathways. They are the key targets for cellular reactive oxygen species (ROS), acting as signaling switches between ROS and ionic homeostasis. We have carried out a paraquat (PQ) screen in Drosophila to identify ion channels regulating the ROS handling and survival in Drosophila melanogaster. Our screen has revealed that α1-subunits (D-type, T-type, and cacophony) of voltage-gated calcium channels (VGCCs) handle PQ-mediated ROS stress differentially in a gender-based manner...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29709527/upregulation-of-n-type-calcium-channels-in-the-soma-of-uninjured-dorsal-root-ganglion-neurons-contributes-to-neuropathic-pain-by-increasing-neuronal-excitability-following-peripheral-nerve-injury
#13
Jie Yang, Man-Xiu Xie, Li Hu, Xiao-Fang Wang, Jie-Zhen Mai, Yong-Yong Li, Ning Wu, Cheng Zhang, Jin Li, Rui-Ping Pang, Xian-Guo Liu
N-type voltage-gated calcium (Cav2.2) channels are expressed in the central terminals of dorsal root ganglion (DRG) neurons, and are critical for neurotransmitter release. Cav2.2 channels are also expressed in the soma of DRG neurons, where their function remains largely unknown. Here, we showed that Cav2.2 was upregulated in the soma of uninjured L4 DRG neurons, but downregulated in those of injured L5 DRG neurons following L5 spinal nerve ligation (L5-SNL). Local application of specific Cav2.2 blockers (ω-conotoxin GVIA, 1-100 μM or ZC88, 10-1000 μM) onto L4 and 6 DRGs on the operated side, but not the contralateral side, dose-dependently reversed mechanical allodynia induced by L5-SNL...
April 27, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29707693/catsper-a-unique-calcium-channel-of-the-sperm-flagellum
#14
Polina V Lishko, Nadja Mannowetz
To overcome egg protective vestments and ensure successful fertilization, mammalian spermatozoa switch symmetrical progressive motility to a powerful, whip-like flagellar motion, known as hyperactivation. The latter is triggered by a calcium influx through the sperm-specific, voltage-dependent, and alkalization-activated calcium channel of sperm - CatSper. The channel comprises nine subunits which together form a heteromeric complex. CatSper-deficient male mice and men with mutations in CatSper genes are infertile...
April 2018: Current Opinion in Physiology
https://www.readbyqxmd.com/read/29704483/the-potent-insulin-secretagogue-effect-of-betulinic-acid-is-mediated-by-potassium-and-chloride-channels
#15
Allisson Jhonatan Gomes Castro, Luisa Helena Cazarolli, Lizandra C Bretanha, Paola Miranda Sulis, Diana Patricia Rey Padilla, Diana Marcela Aragón Novoa, Betina Fernanda Dambrós, Moacir G Pizzolatti, Fátima Regina Mena Barreto Silva
Betulinic acid (BA) has been described as an insulin secretagogue which may explain its potent antihyperglycemic effect; however, the exact role of BA as an insulinogenic agent is not clear. The aim of this study was to investigate the mechanism of BA on calcium influx and static insulin secretion in pancreatic islets isolated from euglycemic rats. We found that BA triggers calcium influx by a mechanism dependent on ATP-dependent potassium channels and L-type voltage-dependent calcium channels. Additionally, the voltage-dependent and calcium-dependent chloride channels are also involved in the mechanism of BA, probably due to an indirect stimulation of calcium entry and increased intracellular calcium...
April 25, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29703643/medaka-as-a-model-for-ecg-analysis-and-the-effect-of-verapamil
#16
Manabu Yonekura, Nami Kondoh, Chong Han, Yuichi Toyama, Takayoshi Ohba, Kyoichi Ono, Shirou Itagaki, Hirofumi Tomita, Manabu Murakami
The heart of the medaka, a small fish native to East Asia, has electrophysiological aspects similar to mammalian hearts. We found that the heart rates of medaka were more similar to humans than mice or rats. Medaka exhibited similar electrocardiogram patterns to those of humans, suggesting a similarity in cardiac impulse formation and propagation. Their hearts also exhibited similar responsiveness to verapamil, a calcium channel antagonist; atropine, a parasympathetic nerve blocker; propranolol, a sympathetic β-adrenergic blocker; and isoproterenol, a sympathetic β-adrenergic agonist...
April 12, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29694233/functional-features-of-the-finger-domain-of-deg-enac-channels-mec-4-and-unc-8
#17
Cristina Matthewman, Christina K Johnson, David M Miller Iii, Laura Bianchi
UNC-8 and MEC-4 are two members of the DEG/ENaC family of voltage-independent Na+ channels that share a high degree of sequence homology and functional similarity. For example, both can be hyperactivated by genetic mutations (UNC-8(d) and MEC-4(d)) that induce neuronal death by necrosis. Both depend in vivo on chaperone protein MEC-6 for function, as demonstrated by the finding that neuronal death induced by hyperactive UNC-8 and MEC-4 channels is prevented by null mutations in mec-6. UNC-8 and MEC-4 differ functionally in three major ways: 1) MEC-4 is calcium permeable whereas UNC-8 is not; 2) UNC-8, but not MEC-4, is blocked by extracellular calcium and magnesium in the micromolar range; 3) MEC-6 increases the number of MEC-4 channels at the cell surface in oocytes but does not have this effect on UNC-8...
April 25, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29692624/comparative-analysis-of-molecular-signatures-suggests-the-use-of-gabapentin-for-the-management-of-endometriosis-associated-pain
#18
Brice Bellessort, Anne Bachelot, Virginie Grouthier, Camille De Lombares, Nicolas Narboux-Neme, Paolo Garagnani, Chiara Pirazzini, Simonetta Astigiano, Luca Mastracci, Anastasia Fontaine, Gladys Alfama, Evelyne Duvernois-Berthet, Giovanni Levi
Background: It has been repetitively shown that the transcription factors DLX5 and DLX6 are drastically downregulated in endometriotic lesions when compared with eutopic endometrium. These findings suggest that regulatory cascades involving DLX5/6 might be at the origin of endometriosis symptoms such as chronic pelvic pain (CPP). We have shown that inactivation of Dlx5 and Dlx5/6 in the mouse uterus results in an endometrial phenotype reminiscent of endometriosis. Methods: We focused on genes that present a similar deregulation in endometriosis and in Dlx5/6 -null mice in search of new endometriosis targets...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29691127/digenic-heterozigosity-in-scn5a-and-cacna1c-explains-the-variable-expressivity-of-the-long-qt-phenotype-in-a-spanish-family
#19
Paloma Nieto-Marín, Juan Jiménez-Jáimez, David Tinaquero, Silvia Alfayate, Raquel G Utrilla, María Del Mar Rodríguez Vázquez Del Rey, Francesca Perin, Geòrgia Sarquella-Brugada, Lorenzo Monserrat, Josep Brugada, Luis Tercedor, Juan Tamargo, Eva Delpón, Ricardo Caballero
INTRODUCTION AND OBJECTIVES: A known long QT syndrome-related mutation in Nav1.5 cardiac channels (p.R1644H) was found in 4 members of a Spanish family but only 1 of them showed prolongation of the QT interval. In the other 3 relatives, a novel missense mutation in Cav1.2 cardiac channels was found (p.S1961N). Here, we functionally analyzed p.S1961N Cav1.2 channels to elucidate whether this mutation regulates the expressivity of the long QT syndrome phenotype in this family. METHODS: L-type calcium current (ICaL ) recordings were performed by using the whole-cell patch-clamp technique in Chinese hamster ovary cells transiently transfected with native and/or p...
April 21, 2018: Revista Española de Cardiología
https://www.readbyqxmd.com/read/29684385/upregulation-of-ca-v-3-2-t-type-calcium-channels-in-adjacent-intact-l4-dorsal-root-ganglion-neurons-in-neuropathic-pain-rats-with-l5-spinal-nerve-ligation
#20
Qing-Ying Liu, Wen Chen, Shuang Cui, Fei-Fei Liao, Ming Yi, Feng-Yu Liu, You Wan
Besides the injured peripheral dorsal root ganglion (DRG) neurons, the adjacent intact DRG neurons also have important roles in neuropathic pain. Ion channels including Cav 3.2 T-type calcium channel in the DRG neurons are important in the development of neuropathic pain. In the present study, we aimed to examine the expression of Cav 3.2 T-type calcium channels in the intact DRG neurons in neuropathic pain. A neuropathic pain model of rat with lumbar 5 (L5) spinal nerve ligation (SNL) was established, in which the L4 DRG was separated from the axotomized L5 DRG, and the molecular, morphological and electrophysiological changes of Cav 3...
April 20, 2018: Neuroscience Research
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