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L-type of voltage-gated Ca2+ channel

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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
#1
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
#2
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...
July 8, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27554679/carbon-monoxide-potentiation-of-l-type-ca-2-channel-activity-increases-hif-1%C3%AE-independent-vegf-expression-via-an-ampk%C3%AE-sirt1-mediated-pgc-1%C3%AE-err%C3%AE-axis
#12
Yoon Kyung Choi, Ji-Hee Kim, Dong-Keun Lee, Kwang-Soon Lee, Moo-Ho Won, Dooil Jeoung, Hansoo Lee, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
AIMS: The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway induced in astrocytes after ischemic brain injury promotes vascular endothelial growth factor (VEGF) expression to maintain and repair neurovascular function. Although HO-1-derived CO has been shown to induce hypoxia-inducible factor-1α (HIF-1α)-dependent VEGF expression, the underlying mechanism independent of HIF-1α remains to be elucidated. RESULTS: HO-1 and VEGF were coexpressed in astrocytes of ischemic mouse brain tissues...
July 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27405329/differential-regulation-of-human-paired-associative-stimulation-induced-and-theta-burst-stimulation-induced-plasticity-by-l-type-and-t-type-ca2-channels
#13
David Weise, Jakob Mann, Jost-Julian Rumpf, Stefan Hallermann, Joseph Classen
Activity-dependent changes of postsynaptic Ca2+-concentration are influenced by a variety of different Ca2+-channels and play an important role in synaptic plasticity. Paired associative stimulation (PAS) and theta-burst stimulation (TBS) are noninvasive magnetic stimulation protocols used in human subjects to induce lasting corticospinal excitability changes that have been likened to synaptic long-term potentiation and long-term depression. To better characterize the Ca2+-related physiological mechanisms underlying PAS- and TBS-induced plasticity, we examined the impact of different Ca2+-sources...
August 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/27306612/redox-dependent-modulation-of-t-type-ca-2-channels-in-sensory-neurons-contributes-to-acute-anti-nociceptive-effect-of-substance-p
#14
Dongyang Huang, Sha Huang, Haixia Gao, Yani Liu, Jinlong Qi, Pingping Chen, Caixue Wang, Jason L Scragg, Alexander Vakurov, Chris Peers, Xiaona Du, Hailin Zhang, Nikita Gamper
AIMS: Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. RESULTS: SP acutely inhibited T-type voltage-gated Ca(2+) channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS...
August 10, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27270916/cav1-4-l-type-calcium-channels-contribute-to-calpain-activation-in-degenerating-photoreceptors-of-rd1-mice
#15
Christian Schön, François Paquet-Durand, Stylianos Michalakis
Retinitis pigmentosa is an inherited blinding disorder characterized by progressive degeneration and loss of photoreceptors. The exact mechanism of degeneration and cell death of photoreceptors is not known, but is thought to involve disturbed Ca2+-signaling. Ca2+ can enter the photoreceptor cell via outer segment cyclic nucleotide-gated (CNG) channels or synaptic Cav1.4 L-type voltage-gated calcium channels (VGCC). Previously, we have shown that genetic ablation of the Cngb1 gene encoding the B subunit of the rod CNG channel delays the fast progressing degeneration in the rd1 mutant mouse model of retinitis pigmentosa...
2016: PloS One
https://www.readbyqxmd.com/read/27247394/k-atp-channel-gain-of-function-leads-to-increased-myocardial-l-type-ca-2-current-and-contractility-in-cantu-syndrome
#16
Mark D Levin, Gautam K Singh, Hai Xia Zhang, Keita Uchida, Beth A Kozel, Phyllis K Stein, Atilla Kovacs, Ruth E Westenbroek, William A Catterall, Dorothy Katherine Grange, Colin G Nichols
Cantu syndrome (CS) is caused by gain-of-function (GOF) mutations in genes encoding pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) KATP channel subunits. We show that patients with CS, as well as mice with constitutive (cGOF) or tamoxifen-induced (icGOF) cardiac-specific Kir6.1 GOF subunit expression, have enlarged hearts, with increased ejection fraction and increased contractility. Whole-cell voltage-clamp recordings from cGOF or icGOF ventricular myocytes (VM) show increased basal L-type Ca(2+) current (LTCC), comparable to that seen in WT VM treated with isoproterenol...
June 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27232631/control-of-ca2-influx-and-calmodulin-activation-by-sk-channels-in-dendritic-spines
#17
Thom Griffith, Krasimira Tsaneva-Atanasova, Jack R Mellor
The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels) which are in turn inhibited by neuromodulators such as acetylcholine...
May 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27168360/thrombospondin-4-divergently-regulates-voltage-gated-ca2-channel-subtypes-in-sensory-neurons-after-nerve-injury
#18
Bin Pan, Yuan Guo, Hsiang-En Wu, John Park, Van Nancy Trinh, Z David Luo, Quinn H Hogan
Loss of high-voltage-activated (HVA) calcium current (ICa) and gain of low-voltage-activated (LVA) ICa after painful peripheral nerve injury cause elevated excitability in sensory neurons. Nerve injury is also accompanied by increased expression of the extracellular matrix glycoprotein thrombospondin-4 (TSP4), and interruption of TSP4 function can reverse or prevent behavioral hypersensitivity after injury. We therefore investigated TSP4 regulation of ICa in dorsal root ganglion (DRG) neurons. During depolarization adequate to activate HVA ICa, TSP4 decreases both N- and L-type ICa and the associated intracellular calcium transient...
2016: Pain
https://www.readbyqxmd.com/read/26848587/syntaxin-3-binds-and-regulates-both-r-and-l-type-calcium-channels-in-insulin-secreting-ins-1-832-13-cells
#19
Li Xie, Subhankar Dolai, Youhou Kang, Tao Liang, Huanli Xie, Tairan Qin, Lu Yang, Liangyi Chen, Herbert Y Gaisano
Syntaxin (Syn)-1A mediates exocytosis of predocked insulin-containing secretory granules (SGs) during first-phase glucose-stimulated insulin secretion (GSIS) in part via its interaction with plasma membrane (PM)-bound L-type voltage-gated calcium channels (Cav). In contrast, Syn-3 mediates exocytosis of newcomer SGs that accounts for second-phase GSIS. We now hypothesize that the newcomer SG Syn-3 preferentially binds and modulates R-type Cav opening, which was postulated to mediate second-phase GSIS. Indeed, glucose-stimulation of pancreatic islet β-cell line INS-1 induced a predominant increase in interaction between Syn-3 and Cavα1 pore-forming subunits of R-type Cav2...
2016: PloS One
https://www.readbyqxmd.com/read/26673782/smooth-muscle-like-cells-generated-from-human-mesenchymal-stromal-cells-display-marker-gene-expression-and-electrophysiological-competence-comparable-to-bladder-smooth-muscle-cells
#20
Juliane Brun, Katrin A Lutz, Katharina M H Neumayer, Gerd Klein, Tanja Seeger, Tatiana Uynuk-Ool, Katharina Wörgötter, Sandra Schmid, Udo Kraushaar, Elke Guenther, Bernd Rolauffs, Wilhelm K Aicher, Melanie L Hart
The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late) myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs...
2015: PloS One
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