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Cell Calcium

Ibrahim Ramirez-Soto, Eduardo Rodriguez, Rocío Alvarez, Eugenio Quiroz, Alicia Ortega
Carazolol (CZL) is a known agonist of β3 and antagonist of β1 and β2 adrenoceptors (AR), used in the animal production industry to improve meat quality by reducing animal stress and skeletal muscle (SM) proteolysis. Here we sought to better understand the direct effect CZL has on SM. We study CZL effect on calcium (Ca2+ ) regulation by enzymatic activity kinetics of the Ca2+ -ATPase (SERCA), in isolated sarcoplasmic reticulum (SR) from SM and on the mechanical properties of isolated muscle. In isolated SR from SM previously incubated with 0...
February 11, 2019: Cell Calcium
Martin Johnson, Mohamed Trebak
Cardiorespiratory disease, which includes systemic arterial hypertension, restenosis, atherosclerosis, pulmonary arterial hypertension, asthma, and chronic obstructive pulmonary disease (COPD) are highly prevalent and devastating diseases with limited therapeutic modalities. A common pathophysiological theme to these diseases is cellular remodeling, which is contributed by changes in expression and activation of ion channels critical for either excitability or growth. Calcium (Ca2+ ) signaling and specifically ORAI Ca2+ channels have emerged as significant regulators of smooth muscle, endothelial, epithelial, platelet, and immune cell remodeling...
February 8, 2019: Cell Calcium
Tomohiko Kayano, Yuto Sasaki, Naoki Kitamura, Nobuya Harayama, Taiki Moriya, Govindan Dayanithi, Alexei Verkhratsky, Izumi Shibuya
Rat melanotrophs express several types of voltage-gated and ligand-gated calcium channels, although mechanisms involved in the maintenance of the resting intracellular Ca2+ concentration ([Ca2+ ]i ) remain unknown. We analyzed mechanisms regulating resting [Ca2+ ]i in dissociated rat melanotrophs by Ca2+ -imaging and patch-clamp techniques. Treatment with antagonists of L-type, but not N- or P/Q-type voltage-gated Ca2+ channels (VGCCs) as well as removal of extracellular Ca2+ resulted in a rapid and reversible decrease in [Ca2+ ]i , indicating constitutive Ca2+ influx through L-type VGCCs...
February 6, 2019: Cell Calcium
Robin Sachdeva, Thomas Fleming, Dagmar Schumacher, Sarah Homberg, Kathrin Stilz, Franziska Mohr, Andreas H Wagner, Volodymyr Tsvilovskyy, Ilka Mathar, Marc Freichel
Methylglyoxal (MG) is a by-product of glucose metabolism and its accumulation has been linked to the development of diabetic complications such as retinopathy and nephropathy by affecting multiple signalling pathways. However, its influence on the intracellular Ca2+ homeostasis and particularly Ca2+ entry, which has been reported to be mediated via TRPA1 channels in DRG neurons, has not been studied in much detail in other cell types. In this study, we report the consequences of acute and long-term MG application on intracellular Ca2+ levels in endothelial cells...
January 9, 2019: Cell Calcium
Regina A Clemens, Clifford A Lowell
Calcium is a major intracellular signaling messenger in innate immune cells. Similar to other immune cell subsets, the majority of calcium entry into innate immune cells is induced by cell surface receptors that stimulate store-operated calcium entry through calcium-release activated calcium (CRAC) channels. Since the molecular description of the STIM family of calcium sensors and the ORAI family of CRAC channel proteins, the majority of studies support a dominant role for these proteins in calcium signaling in innate cells...
January 9, 2019: Cell Calcium
Akitoshi Miyamoto, Katsuhiko Mikoshiba
Extracellular stimuli evoke a robust increase in the concentration of intracellular Ca2+ ([Ca2+ ]c ) throughout the cell to trigger various cellular responses, such as gene expression and apoptosis. This robust expansion of [Ca2+ ]c is called Ca2+ propagation. To date, it is thought that intracellular second messengers, such as inositol 1,4,5-trisphosphate (IP3 ) and intracellular Ca2+ , and clusters of IP3 receptors (IP3 Rs) regulate Ca2+ propagation. However, little is known about how the elevation in the [Ca2+ ]c spreads throughout the cell, especially in non-polar cell, including HeLa cell...
January 4, 2019: Cell Calcium
Haiping Liu, Ahmed Kabrah, Malini Ahuja, Shmuel Muallem
The receptor-evoked Ca2+ signal in secretory epithelia mediate many cellular functions essential for cell survival and their most fundamental functions of secretory granules exocytosis and fluid and electrolyte secretion. Ca2+ influx is a key component of the receptor-evoked Ca2+ signal in secretory cell and is mediated by both TRPC and the STIM1-activated Orai1 channels that mediates the Ca2+ release-activated current (CRAC) Icrac . The core components of the receptor-evoked Ca2+ signal are assembled at the ER/PM junctions where exchange of materials between the plasma membrane and internal organelles take place, including transfer of lipids and Ca2+ ...
December 31, 2018: Cell Calcium
S Häfner, N Urban, M Schaefer
The non-selective second messenger-gated cation channel TRPC6 (transient receptor potential canonical 6) is activated by diacylglycerols (DAG) in a PKC-independent manner and plays important roles in a variety of physiological processes and diseases. In order to facilitate novel therapies, the development of potent inhibitors as well as channel-activating agents is of great interest. The screening of a chemical library, comprising about 17,000 small molecule compounds, revealed an agent, which induced increases in intracellular Ca2+ concentrations ([Ca2+ ]i ) in a concentration-dependent manner (EC50  = 2...
December 21, 2018: Cell Calcium
Sofia Segal, Noa Kirschner Peretz, Limor Arbel-Ganon, Jinghui Liang, Linlin Li, Daphna Marbach, Dongmei Yang, Shi-Qiang Wang, Yael Yaniv
Pacemaker cells residing in the sinoatrial node generate the regular heartbeat. Ca2+ signaling controls the heartbeat rate-directly, through the effect on membrane molecules (NCX exchange, K+ channel), and indirectly, through activation of calmodulin-AC-cAMP-PKA signaling. Thus, the physiological role of signaling in pacemaker cells can only be assessed if the Ca2+ dynamics are in the physiological range. Cultured cells that can be genetically manipulated and/or virally infected with probes are required for this purpose...
December 18, 2018: Cell Calcium
Alexey Semyanov
Ca2+ influx through an astrocyte plasma membrane is mediated by ionotropic receptors and Ca2+ channels according the electrochemical gradient. These conductances allow astrocytes to sense the levels of neuronal activity and environmental changes. Na+ /Ca2+ exchanger (NCX) removes elevated Ca2+ from the cell but can reverse and bring Ca2+ in. Ca2+ entry through the plasma membrane produces local Ca2+ elevations that can be further amplified by Ca2+ induced activation of inositol-3-phosphate (IP3 ) receptors and subsequent Ca2+ release from intracellular Ca2+ stores...
December 17, 2018: Cell Calcium
José-Carlos Fernández-Morales, Wei Hua, Yuyu Yao, Martin Morad
AIMS: The effects of acute (100 s) hypoxia and/or acidosis on Ca2+ signaling parameters of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are explored here for the first time. METHODS AND RESULTS: 1) hiPSC-CMs express two cell populations: rapidly-inactivating ICa myocytes (τi <40 ms, in 4-5 day cultures) and slowly-inactivating ICa (τi   ≥ 40 ms, in 6-8 day cultures). 2) Hypoxia suppressed ICa by 10-20% in rapidly- and 40-55% in slowly-inactivating ICa cells...
December 12, 2018: Cell Calcium
Jessica Arias-Del-Val, Jaime Santo-Domingo, Paloma García-Casas, Pilar Alvarez-Illera, Antonio Núñez Galindo, Andreas Wiederkehr, Rosalba I Fonteriz, Mayte Montero, Javier Alvarez
The 5' AMP-activated protein kinase (AMPK) is a nutrient-sensitive kinase that plays a key role in the control of cellular energy metabolism. We have explored here the relationship between AMPK and Ca2+ signaling by looking at the effect of an AMPK activator (A769662) and an AMPK inhibitor (dorsomorphin) on histamine-induced Ca2+ -release from the endoplasmic reticulum (ER) in HeLa cells. Our data show that incubation with A769662 (EC50  = 29 μM) inhibited histamine-induced Ca2+ -release from the ER in intact cells, as well as inositol-1,4,5-trisphosphate (IP3 )-induced Ca2+ release in permeabilized cells...
December 11, 2018: Cell Calcium
David J Beech
In a compelling new report Zeng et al. (Science 2018) suggest that neuronal Piezo1 and Piezo2 channels sense blood pressure in major arteries above the heart [1]. The data challenge previous proposed baroreceptor mechanisms and add to prior knowledge of Piezo1 channels as sensors of blood flow and key players generally in cardiovascular biology.
December 11, 2018: Cell Calcium
Christina K Go, Scott Gross, Robert Hooper, Jonathan Soboloff
Ca2+ is a ubiquitous, dynamic and pluripotent second messenger with highly context-dependent roles in complex cellular processes such as differentiation, proliferation, and cell death. These Ca2+ signals are generated by Ca2+ -permeable channels located on the plasma membrane (PM) and endoplasmic reticulum (ER) and shaped by PM- and ER-localized pumps and transporters. Differences in the expression of these Ca2+ homeostasis proteins contribute to cell and context-dependent differences in the spatiotemporal organization of Ca2+ signals and, ultimately, cell fate...
December 6, 2018: Cell Calcium
Simon Chamberland, Alfonsa Zamora Moratalla, Lisa Topolnik
Local circuit GABAergic inhibitory interneurons control the integration and transfer of information in many brain regions. Several different forms of plasticity reported at interneuron excitatory synapses are triggered by cell- and synapse-specific postsynaptic calcium (Ca2+ ) mechanisms. To support this function, the spatiotemporal dynamics of dendritic Ca2+ elevations must be tightly regulated. While the dynamics of postsynaptic Ca2+ signaling through activation of different Ca2+ sources has been explored, the Ca2+ extrusion mechanisms that operate in interneuron dendrites during different patterns of activity remain largely unknown...
December 4, 2018: Cell Calcium
Peter B Stathopulos, Mitsuhiko Ikura
A single calcium (Ca2+ ) binding site within the canonical EF-hand loop was thought to govern the stromal interaction molecule-1 (STIM1) structural changes that lead to activation of Orai1 Ca2+ channels. Recent work by Gudlur et al., published in Nat Commun [9(1):4536], suggests that the STIM1 endoplasmic reticulum (ER) luminal domain has ∼5 additional Ca2+ binding sites, which underlie a surprising new proposal for Ca2+ sensing.
December 3, 2018: Cell Calcium
Paul Rosenberg, Danielle Katz, Victoria Bryson
Store operated Ca2+ entry (SOCE) is an ancient and ubiquitous Ca2+ signaling pathway discovered decades ago, but the function of SOCE in human physiology is only now being revealed. The relevance of this pathway to striated muscle was solidified with the description of skeletal myopathies that result from mutations in STIM1 and Orai1, the two SOCE components. Here, we consider the evidence for STIM1 and SOCE in cardiac muscle and the sinoatrial node. We highlight recent studies revealing a role for STIM1 in cardiac growth in response to developmental and pathologic cues...
November 27, 2018: Cell Calcium
Elmina Mammadova-Bach, Magdolna Nagy, Johan W M Heemskerk, Bernhard Nieswandt, Attila Braun
Cytosolic free calcium (Ca2+ ) is a second messenger regulating a wide variety of functions in blood cells, including adhesion, activation, proliferation and migration. Store-operated Ca2+ entry (SOCE), triggered by depletion of Ca2+ from the endoplasmic reticulum, provides a main mechanism of regulated Ca2+ influx in blood cells. SOCE is mediated and regulated by isoforms of the ion channel proteins ORAI and TRP, and the transmembrane Ca2+ sensors stromal interaction molecules (STIMs), respectively. This report provides an overview of the (patho)physiological importance of SOCE in blood cells implicated in thrombosis and thrombo-inflammation, i...
November 23, 2018: Cell Calcium
Victoria Lunz, Christoph Romanin, Irene Frischauf
A primary calcium (Ca2+ ) entry pathway into non-excitable cells is through the store-operated Ca2+ release activated Ca2+ (CRAC) channel. Ca2+ entry into cells is responsible for the initiation of diverse signalling cascades that affect essential cellular processes like gene regulation, cell growth and death, secretion and gene transcription. Upon depletion of intracellular Ca2+ stores within the endoplasmic reticulum (ER), the CRAC channel opens to refill depleted stores. The two key limiting molecular players of the CRAC channel are the stromal interaction molecule (STIM1) embedded in the ER-membrane and Orai1, residing in the plasma membrane (PM), respectively...
January 2019: Cell Calcium
Cheng Chang, Kai Li, Sinan Jiang, Baoman Li, Liu Cao, Ping Wang
PURPOSE: It has been suggested that FK506 could improve some symptoms of OAB in both clinical settings and animal models; however, its mechanism of action is not well-understood. Here, we investigated the effect of FK506 on TRPC6 in bladder smooth muscle, and explored the possible involvement of TRPC6 in OAB. METHODS: FK506 was injected intraperitoneally into rats in which OAB was induced via BOO, and urodynamic indices were recorded. Rats and human bladder smooth muscle tissues with or without OAB were examined for TRPC6 expression by western blot, RT-PCR and IF staining...
November 17, 2018: Cell Calcium
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