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L-type of voltage-gated Ca2+ channel

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https://www.readbyqxmd.com/read/29288665/intact-calcium-signaling-in-adrenergic-deficient-embryonic-mouse-hearts
#1
Jessica N Peoples, David G Taylor, Alexander N Katchman, Steven N Ebert
Mouse embryos that lack the ability to produce the adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to disruption of the dopamine beta-hydroxylase (Dbh-/-) gene inevitably perish from heart failure during mid-gestation. Since adrenergic stimulation is well-known to enhance calcium signaling in developing as well as adult myocardium, and impairments in calcium signaling are typically associated with heart failure, we hypothesized that adrenergic-deficient embryonic hearts would display deficiencies in cardiac calcium signaling relative to adrenergic-competent controls at a developmental stage immediately preceding the onset of heart failure, which first appears beginning or shortly after mouse embryonic day 10...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29237755/differential-contribution-of-ca2-sources-to-day-and-night-bk-current-activation-in-the-circadian-clock
#2
Joshua P Whitt, Beth A McNally, Andrea L Meredith
Large conductance K+ (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca2+ (Ca2+i). To enable this regulation, BK channels functionally couple to both voltage-gated Ca2+ channels (VGCCs) and channels mediating Ca2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca2+i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca2+i are reduced...
December 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29237245/molecular-mechanisms-and-physiological-relevance-of-rgk-proteins-in-the-heart
#3
REVIEW
U Meza, D Beqollari, R A Bannister
The primary route of Ca2+ entry into cardiac myocytes is via 1,4-dihydropyridine-sensitive, voltage-gated L-type Ca2+ channels. Ca2+ influx through these channels influences duration of action potential and engages excitation-contraction (EC) coupling in both the atria and the myocardium. Members of the RGK (Rad, Rem, Rem2, and Gem/Kir) family of small GTP binding proteins are potent, endogenously-expressed inhibitors of cardiac L-type channels. Although much work has focused on the molecular mechanisms by which RGK proteins inhibit the CaV 1...
December 13, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29228786/oxidative-stress-induces-disruption-of-the-axon-initial-segment
#4
Kareem Clark, Brooke A Sword, Jeffrey L Dupree
The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear...
November 2017: ASN Neuro
https://www.readbyqxmd.com/read/29225069/stimulation-of-b-raf-increases-c-jun-and-c-fos-expression-and-upregulates-ap-1-regulated-gene-transcription-in-insulinoma-cells
#5
Daniel S Langfermann, Oliver G Rössler, Gerald Thiel
Stimulation of pancreatic β-cells with glucose activates the protein kinases B-Raf and extracellular signal-regulated protein kinase that participate in glucose sensing. Inhibition of both kinases results in impairment of glucose-regulated gene transcription. To analyze the signaling pathway controlled by B-Raf, we expressed a conditionally active form of B-Raf in INS-1 insulinoma cells. Here, we show that stimulation of B-Raf strongly activated the transcription factor AP-1 which is accompanied by increased c-Jun and c-Fos promoter activities, an upregulation of c-Jun and c-Fos biosynthesis, and elevated transcriptional activation potentials of c-Jun and c-Fos...
December 7, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29213058/interplay-between-global-and-pathway-specific-synaptic-plasticity-in-ca1-pyramidal-cells
#6
Sven Berberich, Jörg Pohle, Marie Pollard, Janet Barroso-Flores, Georg Köhr
Mechanisms underlying information storage have been depicted for global cell-wide and pathway-specific synaptic plasticity. Yet, little is known how these forms of plasticity interact to enhance synaptic competition and network stability. We examined synaptic interactions between apical and basal dendrites of CA1 pyramidal neurons in mouse hippocampal slices. Bursts (50 Hz) of three action potentials (AP-bursts) paired with preceding presynaptic stimulation in stratum radiatum specifically led to LTP of the paired pathway in adult mice (P75)...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29202453/increased-ca2-signaling-through-cav1-2-promotes-bone-formation-and-prevents-estrogen-deficiency-induced-bone-loss
#7
Chike Cao, Yinshi Ren, Adam S Barnett, Anthony J Mirando, Douglas Rouse, Se Hwan Mun, Kyung-Hyun Park-Min, Amy L McNulty, Farshid Guilak, Courtney M Karner, Matthew J Hilton, Geoffrey S Pitt
While the prevalence of osteoporosis is growing rapidly with population aging, therapeutic options remain limited. Here, we identify potentially novel roles for CaV1.2 L-type voltage-gated Ca2+ channels in osteogenesis and exploit a transgenic gain-of-function mutant CaV1.2 to stem bone loss in ovariectomized female mice. We show that endogenous CaV1.2 is expressed in developing bone within proliferating chondrocytes and osteoblasts. Using primary BM stromal cell (BMSC) cultures, we found that Ca2+ influx through CaV1...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29174591/antidepressants-rescue-stress-induced-disruption-of-synaptic-plasticity-via-serotonin-transporter-independent-inhibition-of-l-type-calcium-channels
#8
Claus Normann, Sibylle Frase, Verena Haug, Gregor von Wolff, Kristin Clark, Patrick Münzer, Alexandra Dorner, Jonas Scholliers, Max Horn, Tanja Vo Van, Gabriel Seifert, Tsvetan Serchov, Knut Biber, Christoph Nissen, Norbert Klugbauer, Josef Bischofberger
BACKGROUND: Long-term synaptic plasticity is a basic ability of the brain to dynamically adapt to external stimuli and regulate synaptic strength and ultimately network function. It is dysregulated by behavioral stress in animal models of depression and in humans with major depressive disorder. Antidepressants have been shown to restore disrupted synaptic plasticity in both animal models and humans; however, the underlying mechanism is unclear. METHODS: We examined modulation of synaptic plasticity by selective serotonin reuptake inhibitors (SSRIs) in hippocampal brain slices from wild-type rats and serotonin transporter (SERT) knockout mice...
October 19, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29149324/pyrethroid-insecticide-cypermethrin-modulates-gonadotropin-synthesis-via-calcium-homeostasis-and-erk1-2-signaling-in-l%C3%AE-t2-mouse-pituitary-cells
#9
Feixue Li, Huihui Ma, Jing Liu
Pyrethroids are a class of widely used insecticides. Cypermethrin (CP) is one of most commonly used pyrethroid insecticides and its residue has been frequently detected in environmental media. Our recent animal study reported that early postnatal exposure to CP induced an increase in serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as well as the expression of gonadotropin subunit genes [chorionic gonadotropin α (CGα), LHβ and FSHβ] in pituitary tissues. In this study, we further investigated the precise mechanism by which CP at concentrations of 1-100 nM affected the synthesis of gonadotropins using a murine pituitary gonadotropic cell line LβT2...
November 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28898995/uncovering-the-arrhythmogenic-potential-of-trpm4-activation-in-atrial-derived-hl-1-cells-using-novel-recording-and-numerical-approaches
#10
Yaopeng Hu, Yubin Duan, Ayako Takeuchi, Lin Hai-Kurahara, Jun Ichikawa, Keizo Hiraishi, Tomohiro Numata, Hiroki Ohara, Gentaro Iribe, Michio Nakaya, Masayuki X Mori, Satoshi Matsuoka, Genshan Ma, Ryuji Inoue
Aims: Transient receptor potential cation channel subfamily melastatin member 4 (TRPM4), a Ca2+-activated nonselective cation channel abundantly expressed in the heart, has been implicated in conduction block and other arrhythmic propensities associated with cardiac remodelling and injury. The present study aimed to quantitatively evaluate the arrhythmogenic potential of TRPM4. Methods and results: Patch clamp and biochemical analyses were performed using expression system and an immortalized atrial cardiomyocyte cell line (HL-1), and numerical model simulation was employed...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28693898/nanosecond-pulsed-electric-fields-depolarize-transmembrane-potential-via-voltage-gated-k-ca-2-and-trpm8-channels-in-u87-glioblastoma-cells
#11
Ryan C Burke, Sylvia M Bardet, Lynn Carr, Sergii Romanenko, Delia Arnaud-Cormos, Philippe Leveque, Rodney P O'Connor
Nanosecond pulsed electric fields (nsPEFs) have a variety of applications in the biomedical and biotechnology industries. Cancer treatment has been at the forefront of investigations thus far as nsPEFs permeabilize cellular and intracellular membranes leading to apoptosis and necrosis. nsPEFs may also influence ion channel gating and have the potential to modulate cell physiology without poration of the membrane. This phenomenon was explored using live cell imaging and a sensitive fluorescent probe of transmembrane voltage in the human glioblastoma cell line, U87 MG, known to express a number of voltage-gated ion channels...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28591378/is-there-a-role-for-voltage-gated-na-channels-in-the-aggressiveness-of-breast-cancer
#12
P Rhana, R R Trivelato, P S L Beirão, J S Cruz, A L P Rodrigues
Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness...
June 5, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28515322/g%C3%AE-%C3%AE-directly-modulates-vesicle-fusion-by-competing-with-synaptotagmin-for-binding-to-neuronal-snare-proteins-embedded-in-membranes
#13
Zack Zurawski, Brian Page, Michael C Chicka, Rebecca L Brindley, Christopher A Wells, Anita M Preininger, Karren Hyde, James A Gilbert, Osvaldo Cruz-Rodriguez, Kevin P M Currie, Edwin R Chapman, Simon Alford, Heidi E Hamm
Gi/o-coupled G protein-coupled receptors can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gβγ-mediated modulation of voltage-gated calcium channels (VGCC), inhibition can also be mediated through the direct interaction of Gβγ subunits with the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gβγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin 1(syt1) for binding sites on t-SNARE...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28481223/ca2-channel-clustering-with-insulin-containing-granules-is-disturbed-in-type-2-diabetes
#14
Nikhil R Gandasi, Peng Yin, Michela Riz, Margarita V Chibalina, Giuliana Cortese, Per-Eric Lund, Victor Matveev, Patrik Rorsman, Arthur Sherman, Morten G Pedersen, Sebastian Barg
Loss of first-phase insulin secretion is an early sign of developing type 2 diabetes (T2D). Ca2+ entry through voltage-gated L-type Ca2+ channels triggers exocytosis of insulin-containing granules in pancreatic β cells and is required for the postprandial spike in insulin secretion. Using high-resolution microscopy, we have identified a subset of docked insulin granules in human β cells and rat-derived clonal insulin 1 (INS1) cells for which localized Ca2+ influx triggers exocytosis with high probability and minimal latency...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28472301/new-gain-of-function-mutation-shows-cacna1d-as-recurrently-mutated-gene-in-autism-spectrum-disorders-and-epilepsy
#15
Alexandra Pinggera, Luisa Mackenroth, Andreas Rump, Jens Schallner, Filippo Beleggia, Bernd Wollnik, Jörg Striessnig
CACNA1D encodes the pore-forming α1-subunit of Cav1.3, an L-type voltage-gated Ca2+-channel. Despite the recent discovery of two de novo missense gain-of-function mutations in Cav1.3 in two individuals with autism spectrum disorder (ASD) and intellectual disability CACNA1D has not been considered a prominent ASD-risk gene in large scale genetic analyses, since such studies primarily focus on likely-disruptive genetic variants. Here we report the discovery and characterization of a third de novo missense mutation in CACNA1D (V401L) in a patient with ASD and epilepsy...
August 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28472069/detection-of-trpv4-channel-current-like-activity-in-fawn-hooded-hypertensive-fhh-rat-cerebral-arterial-muscle-cells
#16
Debebe Gebremedhin, David X Zhang, Dorothee Weihrauch, Nnamdi N Uche, David R Harder
The transient receptor potential vallinoid type 4 (TRPV4) is a calcium entry channel known to modulate vascular function by mediating endothelium-dependent vasodilation. The present study investigated if isolated cerebral arterial myocytes of the Fawn Hooded hypertensive (FHH) rat, known to display exaggerated KCa channel current activity and impaired myogenic tone, express TRPV4 channels at the transcript and protein level and exhibit TRPV4-like single-channel cationic current activity. Reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunostaining analysis detected the expression of mRNA transcript and translated protein of TRPV4 channel in FHH rat cerebral arterial myocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28324107/functional-characterization-of-transient-receptor-potential-trp-channel-c5-in-female-murine-gonadotropes
#17
Andreas Beck, Viktoria Götz, Sen Qiao, Petra Weissgerber, Veit Flockerzi, Marc Freichel, Ulrich Boehm
Gonadotrope cells in the anterior pituitary gland secrete gonadotropins regulating gonadal function in mammals. Recent results have implicated transient receptor potential (TRP) cation channels in pituitary physiology; however, if and how TRP channels contribute to gonadotrope function is not known. Here, we report that 14 out of 28 TRP channels encoded in the mouse genome are expressed in murine gonadotropes with highest expression levels found for canonical TRP (TRPC) channel 5 in juvenile females. We show that TRP channel expression in these cells exhibits considerable plasticity and that it depends on the sex and the developmental and hormonal status of the animal...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/27986922/cocaine-promotes-coincidence-detection-and-lowers-induction-threshold-during-hebbian-associative-synaptic-potentiation-in-prefrontal-cortex
#18
Hongyu Ruan, Wei-Dong Yao
Addictive drugs usurp neural plasticity mechanisms that normally serve reward-related learning and memory, primarily by evoking changes in glutamatergic synaptic strength in the mesocorticolimbic dopamine circuitry. Here we show that repeated cocaine exposure in vivo does not alter synaptic strength in the mouse prefrontal cortex during an early period of withdrawal, but instead modifies a Hebbian quantitative synaptic learning rule by broadening the temporal window and lowers the induction threshold for spike timing-dependent LTP (t-LTP)...
December 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27624941/regulation-of-l-type-ca2-channel-activity-and-insulin-secretion-by-huntingtin-associated-protein-1
#19
Jing-Ying Pan, Shijin Yuan, Tao Yu, Cong-Lin Su, Xiao-Long Liu, Jun He, He Li
Huntingtin-associated protein 1 (Hap1) was originally identified as a protein that binds to the Huntington disease protein, huntingtin. Growing evidence has shown that Hap1 participates in intracellular trafficking via its association with various microtubule-dependent transporters and organelles. Recent studies also revealed that Hap1 is involved in exocytosis such as insulin release from pancreatic β-cells. However, the mechanism underlying the action of Hap1 on insulin release remains to be investigated...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27587775/measuring-ca2-dependent-modulation-of-voltage-gated-ca2-channels-in-hek-293t-cells
#20
Jessica R Thomas, Amy Lee
Voltage-gated Ca(2+) (Cav) channels regulate a variety of biological processes, such as muscle contraction, gene expression, and neurotransmitter release. Cav channels are subject to diverse forms of regulation, including those involving the Ca(2+) ions that permeate the pore. High voltage-activated Cav channels undergo Ca(2+)-dependent inactivation (CDI) and facilitation (CDF), which can regulate processes such as cardiac rhythm and synaptic plasticity. CDI and CDF differ slightly between Cav1 (L-type) and Cav2 (P/Q-, N-, and R-type) channels...
September 1, 2016: Cold Spring Harbor Protocols
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