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https://www.readbyqxmd.com/read/28295232/cav-1-3-channels-play-a-crucial-role-in-the-formation-of-paroxysmal-depolarization-shifts-in-cultured-hippocampal-neurons
#1
Victoria Stiglbauer, Matej Hotka, Manuel Ruiß, Karlheinz Hilber, Stefan Boehm, Helmut Kubista
OBJECTIVE: An increase of neuronal Cav 1.3 L-type calcium channels (LTCCs) has been observed in various animal models of epilepsy. However, LTCC inhibitors failed in clinical trials of epileptic treatment. There is compelling evidence that paroxysmal depolarization shifts (PDSs) involve Ca(2+) influx through LTCCs. PDSs represent a hallmark of epileptiform activity. In recent years, a probable epileptogenic role for PDSs has been proposed. However, the implication of the two neuronal LTCC isoforms, Cav 1...
March 11, 2017: Epilepsia
https://www.readbyqxmd.com/read/28289693/cav1-2-channels-mediate-persistent-chronic-stress-induced-behavioral-deficits-that-are-associated-with-prefrontal-cortex-activation-of-the-p25-cdk5-glucocorticoid-receptor-pathway
#2
Charlotte C Bavley, Delaney K Fischer, Bryant K Rizzo, Anjali M Rajadhyaksha
Chronic stress is known to precipitate and exacerbate neuropsychiatric symptoms, and exposure to stress is particularly pathological in individuals with certain genetic predispositions. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene CACNA1C, which codes for the Cav1.2 subunit of the L-type calcium channel (LTCC), as a common risk variant for multiple neuropsychiatric conditions. Cav1.2 channels mediate experience-dependent changes in gene expression and long-term synaptic plasticity through activation of downstream calcium signaling pathways...
December 2017: Neurobiology of Stress
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#3
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28239561/regulation-of-cardiac-cacnb2-by-microrna-499-potential-role-in-atrial-fibrillation
#4
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
#5
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/28202717/%C3%AE-adrenoceptor-activation-enhances-l-type-calcium-channel-currents-in-anterior-piriform-cortex-pyramidal-cells-of-neonatal-mice-implication-for-odor-learning
#6
Abhinaba Ghosh, Bandhan Mukherjee, Xihua Chen, Qi Yuan
Early odor preference learning occurs in one-week-old rodents when a novel odor is paired with a tactile stimulation mimicking maternal care. β-Adrenoceptors and L-type calcium channels (LTCCs) in the anterior piriform cortex (aPC) are critically involved in this learning. However, whether β-adrenoceptors interact directly with LTCCs in aPC pyramidal cells is unknown. Here we show that pyramidal cells expressed significant LTCC currents that declined with age. β-Adrenoceptor activation via isoproterenol age-dependently enhanced LTCC currents...
March 2017: Learning & Memory
https://www.readbyqxmd.com/read/28186690/reduced-levels-of-cacna1c-attenuate-mesolimbic-dopamine-system-function
#7
Chantelle E Terrillion, David T Dao, Roger Cachope, Mary Kay Lobo, Adam C Puche, Joseph F Cheer, Todd D Gould
Genetic variation in CACNA1C, which codes for the L-type calcium channel (LTCC) Cav 1.2, is associated with clinical diagnoses of bipolar disorder, depression, and schizophrenia. Dysregulation of the mesolimbic dopamine (DA) system is linked to these syndromes and LTCCs are required for normal DAergic neurotransmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc). It is unclear, however, how variations in CACNA1C genotype, and potential subsequent changes in expression levels in these regions, modify risk...
February 10, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28185965/cav1-2-but-not-cav1-3-l-type-calcium-channel-subtype-mediates-nicotine-induced-conditioned-place-preference-in-miceo
#8
Yudan Liu, Meghan Harding, Jules Dore, Xihua Chen
Nicotine use is one of the most common forms of drug addiction. Although L-type calcium channels (LTCCs) are involved in nicotine addiction, the contribution of the two primary LTCC subtypes (Cav1.2 and 1.3) is unknown. This study aims to determine the contribution of these two LTCC subtypes to nicotine-induced conditioned place preference (CPP) responses by using transgenic mouse models that do not express Cav1.3 (Cav1.3(-/-)) or contain a mutation in the dihydropyridine (DHP) site of the Cav1.2 (Cav1.2DHP(-/-))...
April 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28091657/zinc-transport-and-the-inhibition-of-the-l-type-calcium-channel-are-two-separable-functions-of-znt-1
#9
Eden Shusterman, Ofer Beharier, Shiri Levy, Raz Zarivach, Yoram Etzion, Craig R Campbell, Il-Ha Lee, Anuwat Dinudom, David I Cook, Asher Peretz, Amos Katz, Daniel Gitler, Arie Moran
Traditionally, proteins are considered to perform a single role, be it as an enzyme, a channel, a transporter or as a structural scaffold. However, recent studies have described moonlighting proteins that perform distinct and independent functions; for example, TRPM7 is both an ion channel and a kinase. ZnT-1 is a member of the Carrier Diffusion Facilitator family that is expressed throughout the phylogenetic tree from bacteria to humans. Since its cloning in 1995, ZnT-1 is considered a major extruder of Zn(2+) based on its capability to protect cells against zinc toxicity...
January 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28056022/l-type-calcium-channel-inhibition-contributes-to-the-proarrhythmic-effects-of-aconitine-in-human-cardiomyocytes
#10
Jianjun Wu, Xiangchong Wang, Ying Ying Chung, Cai Hong Koh, Zhenfeng Liu, Huicai Guo, Qiang Yuan, Chuan Wang, Suwen Su, Heming Wei
Aconitine (ACO) is well-known for causing lethal ventricular tachyarrhythmias. While cardiac Na+ channel opening during repolarization has long been documented in animal cardiac myocytes, the cellular effects and mechanism of ACO in human remain unexplored. This study aimed to assess the proarrhythmic effects of ACO in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). ACO concentration-dependently (0.3 ~ 3.0 μM) shortened the action potentials (AP) durations (APD) in ventricular-like hiPSC-CMs by > 40% and induced delayed after-depolarization...
2017: PloS One
https://www.readbyqxmd.com/read/28039202/caveolae-specific-activation-loop-between-camkii-and-l-type-ca2-channel-aggravates-cardiac-hypertrophy-in-%C3%AE-1-adrenergic-stimulation
#11
Kota Tonegawa, Wataru Otsuka, Shohei Kumagai, Sachi Matsunami, Nao Hayamizu, Shota Tanaka, Kazumasa Moriwaki, Masanori Obana, Makiko Maeda, Michio Asahi, Hiroshi Kiyonari, Yasushi Fujio, Hiroyuki Nakayama
AIMS: Activation of CaMKII induces a myriad of biological processes and plays dominant roles in cardiac hypertrophy. Caveolar microdomain contains many CaMKII targets, including L-type Ca2+ channel (LTCC) complex, and serves as a signalling platform. The location of CaMKII activation is thought to be critical, however, the roles of CaMKII in caveolae are still elusive due to lack of methodology for the assessment of caveolae-specific activation. Our aim was to develop a novel tool for the specific analysis of CaMKII activation in caveolae, and to determine the functional role of caveolar CaMKII in cardiac hypertrophy...
December 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27922594/cacna1c-in-the-prefrontal-cortex-regulates-depression-related-behaviors-via-redd1
#12
Zeeba D Kabir, Anni S Lee, Caitlin E Burgdorf, Delaney Fischer, Aditi M Rajadhyaksha, Ethan Mok, Bryant Rizzo, Richard C Rice, Kamalpreet Singh, Kristie T Ota, Danielle M Gerhard, Kathryn C Schierberl, Michael Glass, Ronald S Duman, Anjali M Rajadhyaksha
The CACNA1C gene that encodes the L-type Ca(2+) channel (LTCC) Cav1.2 subunit has emerged as a candidate risk gene for multiple neuropsychiatric disorders including bipolar disorder, major depressive disorder and schizophrenia, all marked with depression-related symptoms. Although cacna1c heterozygous (HET) mice have been previously reported to exhibit an antidepressant-like phenotype, the molecular and circuit-level dysfunction remains unknown. Here we report that viral vector-mediated deletion of cacna1c in the adult prefrontal cortex (PFC) of mice recapitulates the antidepressant-like effect observed in cacna1c HET mice using the sucrose preference test (SPT), the forced swim test (FST), and the tail suspension test (TST)...
December 6, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27915047/physical-and-functional-interaction-of-snapin-with-cav1-3-calcium-channel-impacts-channel-protein-trafficking-in-atrial-myocytes
#13
Xiao-Li Sun, Ju-Fang Yuan, Tao Jin, Xiao-Qing Cheng, Qiang Wang, Jia Guo, Wei Zhang, Yin Zhang, Ling Lu, Zhao Zhang
The L-type Ca(2+) channel (LTCC) Cav1.3 plays a critical role in generating electrical activity in atrial myocytes and cardiac pacemaker cells. However, the molecular and functional basis of Cav1.3 modulation in atrial myocytes has not yet been fully understood. By using the yeast two-hybrid system (Y2H), a Cav1.3-associated protein was screened, which was identified as Snapin. Physical interaction and co-localization between Snapin and Cav1.3 were then confirmed in both the heterologous expression system and mouse atrial myocytes...
January 2017: Cellular Signalling
https://www.readbyqxmd.com/read/27905406/differential-roles-for-l-type-calcium-channel-subtypes-in-alcohol-dependence
#14
Stefanie Uhrig, David Vandael, Andrea Marcantoni, Nina Dedic, Ainhoa Bilbao, Miriam A Vogt, Natalie Hirth, Laura Broccoli, Rick E Bernardi, Kai Schönig, Peter Gass, Dusan Bartsch, Rainer Spanagel, Jan M Deussing, Wolfgang H Sommer, Emilio Carbone, Anita C Hansson
It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol-dependent rats during protracted abstinence and naive controls using in situ hybridization and western blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons...
April 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27900342/cacna1c-protecting-young-hippocampal-neurons-in-the-adult-brain
#15
Héctor De Jesús-Cortés, Anjali M Rajadhyaksha, Andrew A Pieper
Neuropsychiatric disease is the leading cause of disability in the United States, and fourth worldwide.(1,2) Not surprisingly, human genetic studies have revealed a common genetic predisposition for many forms of neuropsychiatric disease, potentially explaining why overlapping symptoms are commonly observed across multiple diagnostic categories. For example, the CACNA1C gene was recently identified in the largest human genome-wide association study to date as a risk loci held in common across 5 major forms of neuropsychiatric disease: bipolar disorder, schizophrenia, major depressive disorder (MDD), autism spectrum disorder and attention deficit-hyperactivity disorder...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27888388/cardiac-bin1-cbin1-is-a-regulator-of-cardiac-contractile-function-and-an-emerging-biomarker-of-heart-muscle-health
#16
REVIEW
Kang Zhou, Tingting Hong
In recent decades, a cardiomyocyte membrane scaffolding protein bridging integrator 1 (BIN1) has emerged as a critical multifunctional regulator of transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes. Encoded by a single gene with 20 exons that are alternatively spliced, more than ten BIN1 protein isoforms are expressed with tissue and disease specificity. The recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or BIN1+13+17) plays a crucial role in organizing membrane microfolds within cardiac t-tubules...
November 23, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27881847/epigenetic-regulation-of-l-type-voltage-gated-ca-2-channels-in-mesenteric-arteries-of-aging-hypertensive-rats
#17
Jingwen Liao, Yanyan Zhang, Fang Ye, Lin Zhang, Yu Chen, Fanxing Zeng, Lijun Shi
Accumulating evidence has shown that epigenetic regulation is involved in hypertension and aging. L-type voltage-gated Ca(2+) channels (LTCCs), the dominant channels in vascular myocytes, greatly contribute to arteriole contraction and blood pressure (BP) control. We investigated the dynamic changes and epigenetic regulation of LTCC in the mesenteric arteries of aging hypertensive rats. LTCC function was evaluated by using microvascular rings and whole-cell patch-clamp in the mesenteric arteries of male Wistar-Kyoto rats and spontaneously hypertensive rats at established hypertension (3 month old) and an aging stage (16 month old), respectively...
November 24, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/27823846/genetically-heterogeneous-mice-show-age-related-vision-deficits-not-related-to-increased-rod-cell-l-type-calcium-channel-function-in%C3%A2-vivo
#18
Bruce A Berkowitz, Richard A Miller, Robin Roberts
Visual performance declines over time in humans and 2-18 months outbred Long-Evans (LE) rats; vision is maintained in inbred 2-18 months C57BL/6 (B6) mice. Increased rod L-type calcium channel (LTCC) function predicts visual decline in LE rats but does not occur in B6 mice. Genetic diversity may contribute to rod LTCC function escalation time. To test this hypothesis, 4 and 18 months genetically heterogeneous UM-HET3 mice were studied. Rod LTCC function (manganese-enhanced magnetic resonance imaging [MRI]) and ocular anatomy (MRI, optical coherence tomography) were measured in vivo...
January 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/27798760/rad-deletion-phenocopies-tonic-sympathetic-stimulation-of-the-heart
#19
Bryana M Levitan, Janet R Manning, Catherine N Withers, Jeffrey D Smith, Robin M Shaw, Douglas A Andres, Vincent L Sorrell, Jonathan Satin
Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad(-/-)) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad(-/-) confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad(-/-)...
December 2016: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/27796576/cardiac-inotropy-lusitropy-and-ca-2-handling-with-major-metabolic-substrates-in-rat-heart
#20
Zai Hao Zhao, Jae Boum Youm, Yue Wang, Jeong Hoon Lee, Jae Hwi Sung, Joon-Chul Kim, Sun Hee Woo, Chae Hun Leem, Sung Joon Kim, Lan Cui, Yin Hua Zhang
Fatty acid (FA)-dependent oxidation is the predominant process for energy supply in normal heart. Impaired FA metabolism and metabolic insufficiency underlie the failing of the myocardium. So far, FA metabolism in normal cardiac physiology and heart failure remains undetermined. Here, we evaluate the mechanisms of FA and major metabolic substrates (termed NF) on the contraction, relaxation, and Ca(2+) handling in rat left ventricular (LV) myocytes. Our results showed that NF significantly increased myocyte contraction and facilitated relaxation...
November 2016: Pflügers Archiv: European Journal of Physiology
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