scholarly journals Oscillatory cytosolic calcium waves independent of stimulated inositol 1,4,5-trisphosphate formation in hepatocytes

1991 ◽  
Vol 266 (19) ◽  
pp. 12272-12282 ◽  
Author(s):  
T.A. Rooney ◽  
D.C. Renard ◽  
E.J. Sass ◽  
A.P. Thomas
Keyword(s):  
Cytosolic Calcium ◽  
Calcium Waves ◽  
Inositol 1,4,5 Trisphosphate

TRAVELLING CALCIUM WAVES IN SYSTEMS WITH NON-DIFFUSING BUFFERS

2008 ◽  
Vol 18 (06) ◽  
pp. 883-912 ◽  
Author(s):  
BOGDAN KAZMIERCZAK ◽  
VITALY VOLPERT
Keyword(s):  
Structural Stability ◽  
Diffusion Coefficients ◽  
Calcium Concentration ◽  
Travelling Waves ◽  
Cytosolic Calcium ◽  
Calcium Waves ◽  
Cytosolic Calcium Concentration

The existence and structural stability of travelling waves of systems of the free cytosolic calcium concentration in the presence of immobile buffers are studied. The proof is carried out by passing to zero with the diffusion coefficients of buffers. Thus, its method is different from Ref. 13 where the existence is proved straightforwardly.

scholarly journals Ryanodine receptor gating controls generation of diastolic calcium waves in cardiac myocytes

2015 ◽  
Vol 145 (6) ◽  
pp. 489-511 ◽  
Author(s):  
Pavol Petrovič ◽  
Ivan Valent ◽  
Elena Cocherová ◽  
Jana Pavelková ◽  
Alexandra Zahradníková
Keyword(s):  
Ryanodine Receptor ◽  
Calcium Sensitivity ◽  
Cytosolic Calcium ◽  
Calcium Waves ◽  
Calcium Sparks ◽  
Calcium Spark ◽  
Gating Model ◽  
Calcium Diffusion ◽  
Confocal Scanning ◽  
Deterministic Description

The role of cardiac ryanodine receptor (RyR) gating in the initiation and propagation of calcium waves was investigated using a mathematical model comprising a stochastic description of RyR gating and a deterministic description of calcium diffusion and sequestration. We used a one-dimensional array of equidistantly spaced RyR clusters, representing the confocal scanning line, to simulate the formation of calcium sparks. Our model provided an excellent description of the calcium dependence of the frequency of diastolic calcium sparks and of the increased tendency for the production of calcium waves after a decrease in cytosolic calcium buffering. We developed a hypothesis relating changes in the propensity to form calcium waves to changes of RyR gating and tested it by simulation. With a realistic RyR gating model, increased ability of RyR to be activated by Ca2+ strongly increased the propensity for generation of calcium waves at low (0.05–0.1-µM) calcium concentrations but only slightly at high (0.2–0.4-µM) calcium concentrations. Changes in RyR gating altered calcium wave formation by changing the calcium sensitivity of spontaneous calcium spark activation and/or the average number of open RyRs in spontaneous calcium sparks. Gating changes that did not affect RyR activation by Ca2+ had only a weak effect on the propensity to form calcium waves, even if they strongly increased calcium spark frequency. Calcium waves induced by modulating the properties of the RyR activation site could be suppressed by inhibiting the spontaneous opening of the RyR. These data can explain the increased tendency for production of calcium waves under conditions when RyR gating is altered in cardiac diseases.

Stimulation of Ca2+ influx in αT3–1 gonadotrophs via the cAMP/PKA signaling system

1997 ◽  
Vol 273 (5) ◽  
pp. E850-E858 ◽  
Author(s):  
Marjan Hezareh ◽  
Werner Schlegel ◽  
Stephen R. Rawlings
Keyword(s):  
Adenylate Cyclase ◽  
Calcium Concentration ◽  
Cytosolic Calcium ◽  
Camp Signaling ◽  
Signaling System ◽  
Cyclic Monophosphate ◽  
Pituitary Adenylate Cyclase ◽  
Inositol 1,4,5 Trisphosphate ◽  
Made In ◽  
Stimulation Of

To investigate the regulation of free cytosolic calcium concentration ([Ca2+]i) by the adenosine 3′,5′-cyclic monophosphate (cAMP) signaling system in clonal gonadotrophs, microfluorimetric recordings were made in single indo 1-loaded αT3–1 cells. Forskolin, 8-bromoadenosine 3′,5′-cyclic monophosphate, or a low concentration (100 pM) of the hypothalamic factor pituitary adenylate cyclase-activating polypeptide (PACAP) stimulated Ca2+ step responses or repetitive Ca2+ transients, which were blocked by the removal of extracellular Ca2+ by the dihydropyridine (DHP) (+)PN 200–110 or by preincubation with the protein kinase A (PKA) antagonist H-89 (10 μM). Thus activation of the cAMP/PKA system in αT3–1 gonadotrophs stimulates Ca2+ influx through DHP-sensitive (L-type) Ca2+ channels. In contrast, high PACAP concentrations (100 nM) stimulated biphasic Ca2+ spike-plateau responses. The Ca2+ spike was independent of extracellular Ca2+, and similar responses were observed by microperfusion of individual cells withd- myo-inositol 1,4,5-trisphosphate, suggesting the involvement of the phospholipase C (PLC) signaling pathway. The Ca2+plateau depended on Ca2+ influx, was blocked by (+)PN 200–110, but was only partially blocked by H-89 pretreatment. In conclusion, PACAP stimulates [Ca2+]iincreases in αT3–1 gonadotrophs through both the PLC and adenylate cyclase signaling pathways. Furthermore, this is the first clear demonstration that the cAMP/PKA system can mediate changes in [Ca2+]iin gonadotroph-like cells.

scholarly journals Gαq/11-mediated intracellular calcium responses to retrograde flow in endothelial cells

2012 ◽  
Vol 303 (4) ◽  
pp. C467-C473 ◽  
Author(s):  
Benoît Melchior ◽  
John A. Frangos
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Flow Direction ◽  
Cytosolic Calcium ◽  
Cell Junction ◽  
Retrograde Flow ◽  
Endoplasmic Reticulum Calcium ◽  
Time To Peak ◽  
Inositol 1,4,5 Trisphosphate

Disturbed flow patterns, including reversal in flow direction, are key factors in the development of dysfunctional endothelial cells (ECs) and atherosclerotic lesions. An almost immediate response of ECs to fluid shear stress is the increase in cytosolic calcium concentration ([Ca2+]i). Whether the source of [Ca2+]i is extracellular, released from Ca2+ intracellular stores, or both is still undefined, though it is likely dependent on the nature of forces involved. We have previously shown that a change in flow direction (retrograde flow) on a flow-adapted endothelial monolayer induces the remodeling of the cell-cell junction along with a dramatic [Ca2+]i burst compared with cells exposed to unidirectional or orthograde flow. The heterotrimeric G protein-α q and 11 subunit (Gαq/11) is a likely candidate in effecting shear-induced increases in [Ca2+]i since its expression is enriched at the junction and has been previously shown to be activated within seconds after onset of flow. In flow-adapted human ECs, we have investigated to what extent the Gαq/11 pathway mediates calcium dynamics after reversal in flow direction. We observed that the elapsed time to peak [Ca2+]i response to a 10 dyn/cm2 retrograde shear stress was increased by 11 s in cells silenced with small interfering RNA directed against Gαq/11. A similar lag in [Ca2+]i transient was observed after cells were treated with the phospholipase C (PLC)-βγ inhibitor, U-73122, or the phosphatidylinositol-specific PLC inhibitor, edelfosine, compared with controls. Lower levels of inositol 1,4,5-trisphosphate accumulation seconds after the onset of flow correlated with the increased lag in [Ca2+]i responses observed with the different treatments. In addition, inhibition of the inositol 1,4,5-trisphosphate receptor entirely abrogated flow-induced [Ca2+]i. Taken together, our results identify the Gαq/11-PLC pathway as the initial trigger for retrograde flow-induced endoplasmic reticulum calcium store release, thereby offering a novel approach to regulating EC dysfunctions in regions subjected to the reversal of blood flow.

Mechanism of phorbol ester inhibition of histamine-induced IP3 formation in cultured airway smooth muscle

1989 ◽  
Vol 257 (4) ◽  
pp. L209-L216 ◽  
Author(s):  
R. K. Murray ◽  
C. F. Bennett ◽  
S. J. Fluharty ◽  
M. I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Calcium Release ◽  
Calcium Sensitivity ◽  
Cytosolic Calcium ◽  
Guanine Nucleotide ◽  
Intact Cells ◽  
Kinase C ◽  
Inositol 1,4,5 Trisphosphate ◽  
Site Of Action

Cytosolic calcium is a key determinant of the contractile state of airway smooth muscle (ASM). To investigate the mechanisms by which histamine affects cytosolic calcium, we measured changes in inositol 1,4,5-trisphosphate (IP3) following the addition of histamine to cultured canine ASM cells. The effect of phorbol 12-myristate 13-acetate (PMA) on IP3 formation was investigated under conditions previously shown to abolish histamine-induced calcium release. In both intact cells and ASM membranes, histamine produced a significant increase in IP3 formation, which was inhibited by PMA. The site of this blockade was investigated by examining the effect of PMA on guanine nucleotide-stimulated IP3 formation and on phosphoinositide-specific phospholipase C (PI-PLC) activity in ASM membranes. Guanine nucleotide-stimulated IP3 formation was inhibited by PMA pretreatment. Membrane-associated PI-PLC activity was also decreased, an effect that was not due simply to a shift in the calcium sensitivity of the enzyme. We conclude that in cultured canine ASM cells, PMA blocks histamine-induced IP3 formation and that this inhibition is caused, in part, by a postreceptor site of action of protein kinase C, possibly via a direct effect on PI-PLC.

Effects of barbiturates on human platelet aggregation differ depending on their chemical structures

2003 ◽  
Vol 81 (8) ◽  
pp. 806-814 ◽  
Author(s):  
Masami Sato ◽  
Hideo Hirakata ◽  
Masahiro Ikeda ◽  
Kazuhiko Fukuda
Keyword(s):  
Platelet Aggregation ◽  
Calcium Concentration ◽  
Light Transmission ◽  
Human Platelet ◽  
Clinical Importance ◽  
Cytosolic Calcium ◽  
Free Calcium ◽  
Chemical Structures ◽  
Human Platelet Aggregation ◽  
Inositol 1,4,5 Trisphosphate

The effects of barbiturates on human platelet function are not fully understood. Since we have already revealed the effects and mechanisms of thiopental, thiamylal, and pentobarbital in platelets, the present study attempted to elucidate (i) the effects of other barbiturates on human platelet aggregation, (ii) the underlying mechanisms, and (iii) the structure–function relationship of barbiturates in platelets. Barbiturates, including amobarbital, butalbital, secobarbital, barbital, phenobarbital, metharbital, and primidone, were examined. Human platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, and (+)-9,11-epithia-11,12-methano-thromboxane A2 (STA2), a thromboxane A2 analog, was measured using an 8-channel light-transmission aggregometer. The cytosolic free calcium concentration ([Ca2+]i) was measured by fluorometer using fura-2 loaded platelets. Inositol 1,4,5-trisphosphate (IP3) formation induced by STA2 was determined by a commercially available IP3 assay kit. Amobarbital, butalbital, and secobarbital suppressed ADP-, epinephrine- and STA2-induced platelet aggregation and the STA2-induced [Ca2+]i increase, even when Ca2+ influx was blocked by Ni2+. However, they did not affect STA2-induced IP3 formation. Barbital, phenobarbital, metharbital, and primidone (up to 1 mM) had no effect on ADP- and epinephrine-induced platelet aggregation. Thus, we conclude that amobarbital, butalbital, and secobarbital inhibit platelet aggregation by suppressing [Ca2+]i increase without affecting IP3 formation. However, these antiaggregatory effects may not have clinical importance, since the barbiturate concentrations used were higher than clinically relevant ones. The other tested barbiturates had no effects on platelet aggregation. The data indicate that the effects of barbiturates on platelet aggregation differ depending on their chemical structures.Key words: platelet aggregation, barbiturates, cytosolic calcium concentration, inositol 1,4,5-trisphosphate.

cGMP abolishes agonist-induced [Ca2+]ioscillations in human bladder epithelial cells

2001 ◽  
Vol 281 (6) ◽  
pp. F1067-F1074 ◽  
Author(s):  
H. Y. Kwan ◽  
Y. Huang ◽  
S. K. Kong ◽  
X. Yao
Keyword(s):  
Epithelial Cells ◽  
Prolonged Exposure ◽  
Specific Inhibitor ◽  
Cytosolic Calcium ◽  
Inhibitory Effect ◽  
Calcium Oscillations ◽  
Protein Kinase G ◽  
Human Bladder ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Ca

First published August 9, 2001; 10.1152/ajprenal.00031.2001.—Cytosolic calcium oscillations may permit cells to respond to information provided by increases in intracellular Ca2+ concentration ([Ca2+]i ) while avoiding prolonged exposure to constantly elevated [Ca2+]i. In this study, we demonstrated that agonists could induce Ca2+oscillations in human bladder epithelial cells. Application of 10 μM acetylcholine or 200 nM bradykinin triggered an initial Ca2+ transient that was followed by periodic [Ca2+]i oscillations. The oscillations did not depend on extracellular Ca2+. 8-Bromoguanosine 3′,5′-cyclic monophosphate abolished acetylcholine- or bradykinin-induced oscillations. Elevation of cellular cGMP by dipyridamole, an inhibitor of cGMP-specific phosphodiesterase, also terminated the [Ca2+]i oscillations. The inhibitory effect of cGMP could be reversed by KT-5823, a highly specific inhibitor of protein kinase G (PKG), suggesting that the action of cGMP was mediated by PKG. Comparison of the effect of cGMP with that of xestospongin C, an inhibitor of the inositol 1,4,5-trisphosphate (IP3) receptor, revealed similarities between the action of cGMP and xestospongin C. Therefore, it is likely that cGMP and PKG may target a signal transduction step(s) linked to IP3 receptor-mediated Ca2+ release.

scholarly journals Propofol Affects Neurodegeneration and Neurogenesis by Regulation of Autophagy via Effects on Intracellular Calcium Homeostasis

2017 ◽  
Vol 127 (3) ◽  
pp. 490-501 ◽  
Author(s):  
Hui Qiao ◽  
Yun Li ◽  
Zhendong Xu ◽  
Wenxian Li ◽  
Zhijian Fu ◽  
...  
Keyword(s):  
Cell Survival ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Calcium Concentration ◽  
Neural Progenitor Cells ◽  
Cytosolic Calcium ◽  
Neural Progenitor ◽  
Mediated Effects ◽  
Proliferation And Differentiation ◽  
Inositol 1,4,5 Trisphosphate

Abstract Background In human cortical neural progenitor cells, we investigated the effects of propofol on calcium homeostasis in both the ryanodine and inositol 1,4,5-trisphosphate calcium release channels. We also studied propofol-mediated effects on autophagy, cell survival, and neuro- and gliogenesis. Methods The dose–response relationship between propofol concentration and duration was studied in neural progenitor cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays. The effects of propofol on cytosolic calcium concentration were evaluated using Fura-2, and autophagy activity was determined by LC3II expression levels with Western blot. Proliferation and differentiation were evaluated by bromodeoxyuridine incorporation and immunostaining with neuronal and glial markers. Results Propofol dose- and time-dependently induced cell damage and elevated LC3II expression, most robustly at 200 µM for 24 h (67 ± 11% of control, n = 12 to 19) and 6 h (2.4 ± 0.5 compared with 0.6 ± 0.1 of control, n = 7), respectively. Treatment with 200 μM propofol also increased cytosolic calcium concentration (346 ± 71% of control, n = 22 to 34). Propofol at 10 µM stimulated neural progenitor cell proliferation and promoted neuronal cell fate, whereas propofol at 200 µM impaired neuronal proliferation and promoted glial cell fate (n = 12 to 20). Cotreatment with ryanodine and inositol 1,4,5-trisphosphate receptor antagonists and inhibitors, cytosolic Ca2+ chelators, or autophagy inhibitors mostly mitigated the propofol-mediated effects on survival, proliferation, and differentiation. Conclusions These results suggest that propofol-mediated cell survival or neurogenesis is closely associated with propofol’s effects on autophagy by activation of ryanodine and inositol 1,4,5-trisphosphate receptors.

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