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Calcium channel subunit

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https://www.readbyqxmd.com/read/28239561/regulation-of-cardiac-cacnb2-by-microrna-499-potential-role-in-atrial-fibrillation
#1
Tian-You Ling, Xiao-Li Wang, Qiang Chai, Tong Lu, John M Stulak, Lyle D Joyce, Richard C Daly, Kevin L Greason, Li-Qun Wu, Win-Kuang Shen, Yong-Mei Cha, Hon-Chi Lee
The L-type calcium channel (LTCC) is one of the major ion channels that are known to be associated with the electrical remodeling of atrial fibrillation (AF). In AF, there is significant downregulation of the LTCC, but the underlying mechanism for such downregulation is not clear. We have previously reported that microRNA-499 (miR-499) is significantly upregulated in patients with permanent AF and that KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), is a target of miR-499...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28230278/deletion-of-psychiatric-risk-gene-cacna1c-impairs-hippocampal-neurogenesis-in-cell-autonomous-fashion
#2
Bianca Völkening, Kai Schönig, Golo Kronenberg, Dusan Bartsch, Tillmann Weber
Ca(2+) is a universal signal transducer which fulfills essential functions in cell development and differentiation. CACNA1C, the gene encoding the alpha-1C subunit (i.e., Cav 1.2) of the voltage-dependent l-type calcium channel (LTCC), has been implicated as a risk gene in a variety of neuropsychiatric disorders. To parse the role of Cav 1.2 channels located on astrocyte-like stem cells and their descendants in the development of new granule neurons, we created Tg(GLAST-CreERT2) /Cacna1c(fl/fl) /RCE:loxP mice, a transgenic tool that allows cell-type-specific inducible deletion of Cacna1c...
February 23, 2017: Glia
https://www.readbyqxmd.com/read/28223480/in-vivo-imaging-reveals-that-pregabalin-inhibits-cortical-spreading-depression-and-propagation-to-subcortical-brain-structures
#3
Stuart M Cain, Barry Bohnet, Jeffrey LeDue, Andrew C Yung, Esperanza Garcia, John R Tyson, Sascha R A Alles, Huili Han, Arn M J M van den Maagdenberg, Piotr Kozlowski, Brian A MacVicar, Terrance P Snutch
Migraine is characterized by severe headaches that can be preceded by an aura likely caused by cortical spreading depression (SD). The antiepileptic pregabalin (Lyrica) shows clinical promise for migraine therapy, although its efficacy and mechanism of action are unclear. As detected by diffusion-weighted MRI (DW-MRI) in wild-type (WT) mice, the acute systemic administration of pregabalin increased the threshold for SD initiation in vivo. In familial hemiplegic migraine type 1 mutant mice expressing human mutations (R192Q and S218L) in the CaV2...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28214378/calcium-signaling-through-l-type-calcium-channels-role-in-pathophysiology-of-spinal-nociceptive-transmission
#4
REVIEW
Olivier Roca-Lapirot, Houda Radwani, Franck Aby, Frédéric Nagy, Marc Landry Pascal Fossat
L-type voltage-gated calcium channels (VGCCs) are ubiquitous channels in the central nervous system. L-type calcium channels (LTCs) are mostly post-synaptic channels regulating neuronal firing and gene expression. They play a role in important physio-pathological processes such as learning and memory, Parkinson's disease, autism and, as recognized more recently, in the pathophysiology of pain processes. Classically, the fundamental role of these channels in cardiovascular functions has limited the use of classical molecules to treat LTC-dependent disorders...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28209764/kcnj11-ablation-is-associated-with-increased-nitro-oxidative-stress-during-ischemia-reperfusion-injury-implications-for-human-ischemic-cardiomyopathy
#5
Bo Zhang, Tatiana Novitskaya, Debra G Wheeler, Zhaobin Xu, Elena Chepurko, Ryan Huttinger, Heng He, Saradhadevi Varadharaj, Jay L Zweier, Yanna Song, Meng Xu, Frank E Harrell, Yan Ru Su, Tarek Absi, Mark J Kohr, Mark T Ziolo, Dan M Roden, Christian M Shaffer, Cristi L Galindo, Quinn S Wells, Richard J Gumina
BACKGROUND: Despite increased secondary cardiovascular events in patients with ischemic cardiomyopathy (ICM), the expression of innate cardiac protective molecules in the hearts of patients with ICM is incompletely characterized. Therefore, we used a nonbiased RNAseq approach to determine whether differences in cardiac protective molecules occur with ICM. METHODS AND RESULTS: RNAseq analysis of human control and ICM left ventricular samples demonstrated a significant decrease in KCNJ11 expression with ICM...
February 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28202907/calpain-1-deletion-impairs-mglur-dependent-ltd-and-fear-memory-extinction
#6
Guoqi Zhu, Victor Briz, Jeff Seinfeld, Yan Liu, Xiaoning Bi, Michel Baudry
Recent studies indicate that calpain-1 is required for the induction of long-term potentiation (LTP) elicited by theta-burst stimulation in field CA1 of hippocampus. Here we determined the contribution of calpain-1 in another type of synaptic plasticity, the long-term depression (LTD) elicited by activation of type-I metabotropic glutamate receptors (mGluR-LTD). mGluR-LTD was associated with calpain-1 activation following T-type calcium channel opening, and resulted in the truncation of a regulatory subunit of PP2A, B56α...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199072/genetic-risk-score-analysis-in-early-onset-bipolar-disorder
#7
Paul E Croarkin, Joan L Luby, Kelly Cercy, Jennifer R Geske, Marin Veldic, Matthew Simonson, Paramjit T Joshi, Karen Dineen Wagner, John T Walkup, Malik M Nassan, Alfredo B Cuellar-Barboza, Leah Casuto, Susan L McElroy, Peter S Jensen, Mark A Frye, Joanna M Biernacka
OBJECTIVE: In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). METHODS: Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria...
February 14, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28197074/the-first-extracellular-linker-is-important-for-several-aspects-of-the-gating-mechanism-of-human-trpa1-channel
#8
Lenka Marsakova, Ivan Barvik, Vlastimil Zima, Lucie Zimova, Viktorie Vlachova
Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28193892/kv1-1-channelopathy-abolishes-presynaptic-spike-width-modulation-by-subthreshold-somatic-depolarization
#9
Umesh Vivekananda, Pavel Novak, Oscar D Bello, Yuri E Korchev, Shyam S Krishnakumar, Kirill E Volynski, Dimitri M Kullmann
Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog-digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193459/epileptiform-activity-and-behavioral-arrests-in-mice-overexpressing-the-calcium-channel-subunit-%C3%AE-2%C3%AE-1
#10
Leonardo C Faria, Feng Gu, Isabel Parada, Ben Barres, Z David Luo, David A Prince
: The alpha2delta-1 subunit (α2δ-1) of voltage-gated calcium channels is a receptor for astrocyte-secreted thrombospondins that promote developmental synaptogenesis.Alpha2delta-1 receptors are upregulated in models of injury-induced peripheral pain and epileptogenic neocortical trauma associated with an enhancement of excitatory synaptic connectivity. These results lead to the hypothesis that overexpression of α2δ-1 alone in neocortex of uninjured transgenic (TG) mice might result in increased excitatory connectivity and consequent cortical hyperexcitability and epileptiform activity...
February 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28179209/administration-of-anabolic-steroid-during-adolescence-induces-long-term-cardiac-hypertrophy-and-increases-susceptibility-to-ischemia-reperfusion-injury-in-adult-wistar-rats
#11
Fernando de Azevedo Cruz Seara, Raiana Andrade Quintanilha Barbosa, Dahienne Ferreira de Oliveira, Diorney Luiz Souza Gran da Silva, Adriana Bastos Carvalho, Andrea Claudia Freitas Ferreira, José Hamilton Matheus Nascimento, Emerson Lopes Olivares
Chronic administration of anabolic androgenic steroids (AAS) in adult rats results in cardiac hypertrophy and increased susceptibility to myocardial ischemia/reperfusion (IR) injury. Molecular analyses demonstrated that hyperactivation of type 1 angiotensin II (AT1) receptor mediates cardiac hypertrophy induced by AAS and also induces down-regulation of myocardial ATP-sensitive potassium channel (KATP), resulting in loss of exercise-induced cardioprotection. Exposure to AAS during adolescence promoted long-term cardiovascular dysfunctions, such as dysautonomia...
February 5, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28167673/ubiquitin-ligase-rnf138-promotes-episodic-ataxia-type-2-associated-aberrant-degradation-of-human-cav2-1-p-q-type-calcium-channels
#12
Ssu-Ju Fu, Chung-Jiuan Jeng, Chia-Hao Ma, Yi-Jheng Peng, Chi-Ming Lee, Ya-Ching Fang, Yi-Ching Lee, Sung-Chun Tang, Meng-Chun Hu, Chih-Yung Tang
: Voltage-gated CaV2.1 channels comprise a pore-forming α1A (CaV2.1) subunit with auxiliary α2δ and β subunits. CaV2.1 channels play an essential role in regulating synaptic signaling. Mutations in the human gene encoding CaV2.1 subunit are associated with the cerebellar disease episodic ataxia type 2 (EA2). Several EA2-causing mutants exhibit impaired protein stability and exert dominant-negative suppression of CaV2.1 wild-type (WT) protein expression via aberrant proteasomal degradation...
February 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28167653/orai1-activates-proliferation-of-lymphatic-endothelial-cells-in-response-to-laminar-flow-through-kr%C3%A3-ppel-like-factors-2-and-4
#13
Dongwon Choi, Eunkyung Park, Eunson Jung, Young Jin Seong, Mingu Hong, Sunju Lee, James Burford, Georgina Gyarmati, Janos Peti-Peterdi, Sonal Srikanth, Yousang Gwack, Chester J Koh, Evgenii Boriushkin, Anne Hamik, Alex K Wong, Young-Kwon Hong
RATIONALE: Lymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown. OBJECTIVE: We aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation. METHODS AND RESULTS: Primary endothelial cells from dermal blood and lymphatic vessels (BECs and LECs) were exposed to low-rate steady laminar flow...
February 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28165042/relationship-between-auxiliary-gamma-subunits-and-mallotoxin-on-bk-channel-modulation
#14
Xin Guan, Qin Li, Jiusheng Yan
The large-conductance, calcium- and voltage-activated K(+)(BK) channel consists of the pore-forming α subunits (BKα) and auxiliary subunits. The auxiliary γ1-3 subunits potently modulate the BK channel by shifting its voltage-dependence of channel activation toward the hyperpolarizing direction by approximately 145 mV (γ1), 100 mV (γ2), and 50 mV (γ3). Mallotoxin is a potent small-molecule BK channel activator. We analyzed the relationship between mallotoxin and the γ subunits in their BK channel-activating effects in membrane patches excised from HEK-293 cells...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28159907/acid-sensing-ion-channels-activated-by-evoked-released-protons-modulate-synaptic-transmission-at-the-mouse-calyx-of-held-synapse
#15
Carlota González-Inchauspe, Francisco J Urbano, Mariano N Di Guilmi, Osvaldo D Uchitel
: Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. A drop in extracellular pH induces transient inward currents (IASIC) in postsynaptic MNTB neurons from wild type (WT) mice. The inhibition of IASIC by psalmotoxin-1 (PcTx1) and the absence of these currents in knock out mice for ASIC-1a subunit (ASIC1a(-/-)) suggest that homomeric ASIC-1a channels are mediating these currents in MNTB neurons...
February 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28137618/astrocyte-neuron-interaction-in-diphenyl-ditelluride-toxicity-directed-to-the-cytoskeleton
#16
Luana Heimfarth, Fernanda da Silva Ferreira, Paula Pierozan, Moara Rodrigues Mingori, José Cláudio Fonseca Moreira, João Batista Teixeira da Rocha, Regina Pessoa-Pureur
Diphenylditelluride (PhTe)2 is a neurotoxin that disrupts cytoskeletal homeostasis. We are showing that different concentrations of (PhTe)2 caused hypophosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) and altered actin organization in co-cultured astrocytes and neurons from cerebral cortex of rats. These mechanisms were mediated by N-methyl-d-aspartate (NMDA) receptors without participation of either L-type voltage-dependent calcium channels (L-VDCC) or metabotropic glutamate receptors...
March 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28132660/grin3b-missense-mutation-as-an-inherited-risk-factor-for-schizophrenia-whole-exome-sequencing-in-a-family-with-a-familiar-history-of-psychotic-disorders
#17
Tobias Hornig, Björn Grüning, Kousik Kundu, Torsten Houwaart, Rolf Backofen, Knut Biber, Claus Normann
Glutamate is the most important excitatory neurotransmitter in the brain. The N-methyl-D-aspartate (NMDA) receptor is a glutamate-gated ionotropic cation channel that is composed of several subunits and modulated by a glycine binding site. Many forms of synaptic plasticity depend on the influx of calcium ions through NMDA receptors, and NMDA receptor dysfunction has been linked to a number of neuropsychiatric disorders, including schizophrenia. Whole-exome sequencing was performed in a family with a strong history of psychotic disorders over three generations...
30, 2017: Genetics Research
https://www.readbyqxmd.com/read/28130356/a-novel-human-camk2a-mutation-disrupts-dendritic-morphology-and-synaptic-transmission-and-causes-asd-related-behaviors
#18
Jason R Stephenson, Xiaohan Wang, Tyler L Perfitt, Walker P Parrish, Brian C Shonesy, Christian R Marks, Douglas P Mortlock, Terunaga Nakagawa, James S Sutcliffe, Roger J Colbran
: Characterizing the functional impact of novel mutations linked to autism spectrum disorder (ASD) provides a deeper mechanistic understanding of the underlying pathophysiological mechanisms. Here we show that a de novo Glu183 to Val (E183V) mutation in the CaMKIIα catalytic domain, identified in a proband diagnosed with ASD, decreases both CaMKIIα substrate phosphorylation and regulatory autophosphorylation, and that the mutated kinase acts in a dominant-negative manner to reduce CaMKIIα-WT autophosphorylation...
January 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28123178/clinical-roles-of-calcium-channel-blockers-in-ischemic-heart-diseases
#19
REVIEW
Daisuke Sueta, Noriaki Tabata, Seiji Hokimoto
Calcium (Ca) channel blockers (CCBs) inhibit Ca(2+) channels in the myocardium or vascular smooth muscle cells, inhibit myocardium contraction, inhibit the impulse conduction system (anti-arrhythmias) and cause vasodilation. New classifications based on subtypes of Ca channels and α1 subunits have been proposed. Moreover, CCBs have pleiotropic effects on coronary spastic angina (CSA), including variant angina, myocardial infarction (MI) and stent thrombosis (ST). Although the roles of CCBs in clinical situations remain unknown, further studies in this field are expected to broaden our understanding...
January 26, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28115397/loss-of-%C3%AE-2%C3%AE-1-calcium-channel-subunit-function-increases-the-susceptibility-for-diabetes
#20
Vincenzo Mastrolia, Sylvia M Flucher, Gerald J Obermair, Mathias Drach, Helene Hofer, Erik Renström, Arnold Schwartz, Jörg Striessnig, Bernhard E Flucher, Petronel Tuluc
Reduced pancreatic β-cell function or mass is the critical problem in developing diabetes. Insulin release from β-cells depends on Ca(2+) influx through high voltage-gated Ca(2+) channels (HVCC). Ca(2+) influx also regulate insulin synthesis, insulin granule priming and contribute to β-cell electrical activity. The HVCC are multi-subunit protein complexes composed of a pore-forming α1 and auxiliary β and α2δ subunits. α2δ is a key regulator of membrane incorporation and function of HVCCs. Here we show that genetic deletion of α2δ-1, the dominant α2δ subunit in pancreatic islets, results in glucose intolerance and diabetes without affecting insulin sensitivity...
January 23, 2017: Diabetes
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