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https://www.readbyqxmd.com/read/27915047/physical-and-functional-interaction-of-snapin-with-cav1-3-calcium-channel-impacts-channel-protein-trafficking-in-atrial-myocytes
#1
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 playsa 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 theheterologous expression system and mouse atrial myocytes...
November 30, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27905406/differential-roles-for-l-type-calcium-channel-subtypes-in-alcohol-dependence
#2
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 naïve controls using in situ hybridization and Western Blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons...
December 1, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27900342/cacna1c-protecting-young-hippocampal-neurons-in-the-adult-brain
#3
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
#4
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
#5
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
#6
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...
September 23, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27798760/rad-deletion-phenocopies-tonic-sympathetic-stimulation-of-the-heart
#7
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(-/-)...
October 31, 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
#8
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
https://www.readbyqxmd.com/read/27789286/effects-of-induced-na-ca-2-exchanger-overexpression-on-the-spatial-distribution-of-l-type-ca-2-channels-and-junctophilin-2-in-pressure-overloaded-hearts
#9
Yoshihiro Ujihara, Satoshi Mohri, Yuki Katanosaka
The Na(+)/Ca(2+) exchanger 1 (NCX1) is an essential Ca(2+) efflux system in cardiomyocytes. Although NCX1 is distributed throughout the sarcolemma, a subpopulation of NCX1 is localized to transverse (T)-tubules. There is growing evidence that T-tubule disorganization is a causal event that shifts the transition from hypertrophy to heart failure (HF). However, the detailed molecular mechanisms have not been clarified. Previously, we showed that induced NCX1 expression in pressure-overloaded hearts attenuates defective excitation-contraction coupling and HF progression...
October 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27739540/nmda-receptors-in-mouse-anterior-piriform-cortex-initialize-early-odor-preference-learning-and-l-type-calcium-channels-engage-for-long-term-memory
#10
Bandhan Mukherjee, Qi Yuan
The interactions of L-type calcium channels (LTCCs) and NMDA receptors (NMDARs) in memories are poorly understood. Here we investigated the specific roles of anterior piriform cortex (aPC) LTCCs and NMDARs in early odor preference memory in mice. Using calcium imaging in aPC slices, LTCC activation was shown to be dependent on NMDAR activation. Either D-APV (NMDAR antagonist) or nifedipine (LTCC antagonist) reduced somatic calcium transients in pyramidal cells evoked by lateral olfactory tract stimulation. However, nifedipine did not further reduce calcium in the presence of D-APV...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27727394/melanopsin-phototransduction-contributes-to-light-evoked-choroidal-expansion-and-rod-l-type-calcium-channel-function-in-vivo
#11
Bruce A Berkowitz, Tiffany Schmidt, Robert H Podolsky, Robin Roberts
Purpose: In humans, rodents, and pigeons, the dark → light transition signals nonretinal brain tissue to increase choroidal thickness, a major control element of choroidal blood flow, and thus of photoreceptor and retinal pigment epithelium function. However, it is unclear which photopigments in the retina relay the light signal to the brain. Here, we test the hypothesis that melanopsin (Opn4)-regulated phototransduction modulates light-evoked choroidal thickness expansion in mice. Methods: Two-month-old C57Bl/6 wild-type (B6), 4- to 5-month-old C57Bl/6/129S6 wild-type (B6 + S6), and 2-month-old melanopsin knockout (Opn4-/-) on a B6 + S6 background were studied...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27725084/calcium-handling-precedes-cardiac-differentiation-to-initiate-the-first-heartbeat
#12
Richard Cv Tyser, Antonio Ma Miranda, Chiann-Mun Chen, Sean M Davidson, Shankar Srinivas, Paul R Riley
The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development. How the initial contractions are established and the downstream consequences of the earliest contractile function on cardiac differentiation and morphogenesis have not been described. Using high-resolution live imaging of mouse embryos, we observed randomly distributed spontaneous asynchronous Ca(2+)-oscillations (SACOs) in the forming cardiac crescent (stage E7.75) prior to overt beating. Nascent contraction initiated at around E8...
October 11, 2016: ELife
https://www.readbyqxmd.com/read/27702573/revealing-calcium-fluxes-by-analyzing-inhibition-dynamics-in-action-potential-clamp
#13
Martin Laasmaa, Rikke Birkedal, Marko Vendelin
In cardiac excitation-contraction coupling (ECC), calcium enters the cytosol via L-type Ca(2+) channels (LTCC) and reverse Na(+)/Ca(2+)-exchange (NCXrev), or is released from the sarcoplasmic reticulum (SR) by Ca(2+)-induced Ca(2+)-release (CICR). The magnitude of Ca(2+) influx via the different pathways varies with the state of the cell and is difficult to assess quantitatively, because changes in Ca(2+) influx through one pathway affects the others. In rainbow trout ventricular myocytes, the role of the SR has been uncertain for decades...
October 1, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27683672/vascular-mineralocorticoid-receptor-regulates-microrna-155-to-promote-vasoconstriction-and-rising-blood-pressure-with-aging
#14
Jennifer J DuPont, Amy McCurley, Ana P Davel, Joseph McCarthy, Shawn B Bender, Kwangseok Hong, Yan Yang, Jeung-Ki Yoo, Mark Aronovitz, Wendy E Baur, Demetra D Christou, Michael A Hill, Iris Z Jaffe
Hypertension is nearly universal yet poorly controlled in the elderly despite proven benefits of intensive treatment. Mice lacking mineralocorticoid receptors in smooth muscle cells (SMC-MR-KO) are protected from rising blood pressure (BP) with aging, despite normal renal function. Vasoconstriction is attenuated in aged SMC-MR-KO mice, thus they were used to explore vascular mechanisms that may contribute to hypertension with aging. MicroRNA (miR) profiling identified miR-155 as the most down-regulated miR with vascular aging in MR-intact but not SMC-MR-KO mice...
September 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27572487/microdomain-specific-modulation-of-l-type-calcium-channels-leads-to-triggered-ventricular-arrhythmia-in-heart-failure
#15
Jose L Sanchez-Alonso, Anamika Bhargava, Thomas O'Hara, Alexey V Glukhov, Sophie Schobesberger, Navneet Bhogal, Markus B Sikkel, Catherine Mansfield, Yuri E Korchev, Alexander R Lyon, Prakash P Punjabi, Viacheslav O Nikolaev, Natalia A Trayanova, Julia Gorelik
RATIONALE: Disruption in subcellular targeting of Ca(2+) signaling complexes secondary to changes in cardiac myocyte structure may contribute to the pathophysiology of a variety of cardiac diseases, including heart failure (HF) and certain arrhythmias. OBJECTIVE: To explore microdomain-targeted remodeling of ventricular L-type Ca(2+) channels (LTCCs) in HF. METHODS AND RESULTS: Super-resolution scanning patch-clamp, confocal and fluorescence microscopy were used to explore the distribution of single LTCCs in different membrane microdomains of nonfailing and failing human and rat ventricular myocytes...
September 30, 2016: Circulation Research
https://www.readbyqxmd.com/read/27535226/orai1-and-trpc1-proteins-co-localize-with-cav1-2-channels-to-form-a-signal-complex-in-vascular-smooth-muscle-cells
#16
Javier Ávila-Medina, Eva Calderón-Sánchez, Patricia González-Rodríguez, Francisco Monje-Quiroga, Juan Antonio Rosado, Antonio Castellano, Antonio Ordóñez, Tarik Smani
Voltage-dependent CaV1.2 L-type Ca(2+) channels (LTCC) are the main route for calcium entry in vascular smooth muscle cells (VSMC). Several studies have also determined the relevant role of store-operated Ca(2+) channels (SOCC) in vascular tone regulation. Nevertheless, the role of Orai1- and TRPC1-dependent SOCC in vascular tone regulation and their possible interaction with CaV1.2 are still unknown. The current study sought to characterize the co-activation of SOCC and LTCC upon stimulation by agonists, and to determine the possible crosstalk between Orai1, TRPC1, and CaV1...
September 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27529477/nitric-oxide-synthase-1-modulates-basal-and-%C3%AE-adrenergic-stimulated-contractility-by-rapid-and-reversible-redox-dependent-s-nitrosylation-of-the-heart
#17
Alejandra Z Vielma, Luisa León, Ignacio C Fernández, Daniel R González, Mauricio P Boric
S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC...
2016: PloS One
https://www.readbyqxmd.com/read/27498200/regulation-and-the-mechanism-of-estrogen-on-cav1-2-gene-in-rat-cultured-cortical-astrocytes
#18
Ling He, Xiao-Tong Hu, Yu-Jie Lai, Yan Long, Lu Liu, Bing-Lin Zhu, Guo-Jun Chen
L-type calcium channel (LTCC) gene Cav1.2 is believed to play an important role in the alteration of Ca(2+) homeostasis in brain astrocytes. Increasing evidence shows that alteration of intracellular Ca(2+) concentration is related to the effect of 17β-estradiol (E2) in a variety of neurophysiological and neuropathological conditions. In this study, we measured immunoreactivity of Cav1.2 protein expression in rat primary cortical astrocytes by using Western blots. We demonstrated that E2 upregulated Cav1.2 expression in a dose- and time-dependent manner and the effect of E2 on Cav1...
October 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27486162/peptidomimetic-targeting-of-cav%C3%AE-2-overcomes-dysregulation-of-the-l-type-calcium-channel-density-and-recovers-cardiac-function
#19
Francesca Rusconi, Paola Ceriotti, Michele Miragoli, Pierluigi Carullo, Nicolò Salvarani, Marcella Rocchetti, Elisa Di Pasquale, Stefano Rossi, Maddalena Tessari, Silvia Caprari, Magali Cazade, Paolo Kunderfranco, Jean Chemin, Marie-Louise Bang, Fabio Polticelli, Antonio Zaza, Giuseppe Faggian, Gianluigi Condorelli, Daniele Catalucci
BACKGROUND: L-type calcium channels (LTCCs) play important roles in regulating cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to and density at the cell surface. Factors influencing the expression, half-life, subcellular trafficking, and gating of LTCCs are therefore critically involved in conditions of cardiac physiology and disease. METHODS: Yeast 2-hybrid screenings, biochemical and molecular evaluations, protein interaction assays, fluorescence microscopy, structural molecular modeling, and functional studies were used to investigate the molecular mechanisms through which the LTCC Cavβ2 chaperone regulates channel density at the plasma membrane...
August 16, 2016: Circulation
https://www.readbyqxmd.com/read/27473611/ca-2-signaling-and-emesis-recent-progress-and-new-perspectives
#20
Weixia Zhong, Andrew J Picca, Albert S Lee, Nissar A Darmani
Cisplatin-like chemotherapeutics cause vomiting via calcium (Ca(2+))-dependent release of multiple neurotransmitters (dopamine, serotonin, substance P, etc.) from the gastrointestinal enterochromaffin cells and/or the brainstem. Intracellular Ca(2+) signaling is triggered by activation of diverse emetic receptors (including tachykininergic NK1, serotonergic 5-HT3, dopaminergic D2, cholinergic M1, or histaminergic H1), whose activation in vomit-competent species can evoke emesis. Other emetogens such as cisplatin, rotavirus NSP4 protein and bacterial toxins can also induce intracellular Ca(2+) elevation...
July 26, 2016: Autonomic Neuroscience: Basic & Clinical
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