Calcium release in HSY cells conforms to a steady-state mechanism involving regulation of the inositol 1,4,5-trisphosphate receptor Ca2+ channel by luminal [Ca2+].

In many cell types, low concentrations of inositol 1,4,5-trisphosphate (IP3) release only a portion of the intracellular IP3-sensitive Ca2+ store, a phenomenon known as "quantal" Ca2+ release. It has been suggested that this effect is a result of reduced activity of the IP3-dependent Ca2+ channel with decreasing calcium concentration within the IP3-sensitive store ([Ca2+]s). To test this hypothesis, the properties of IP3-dependent Ca2+ release in single saponin-permeabilized HSY cells were studied by monitoring [Ca2+]s using the Ca(2+)-sensitive fluorescent dye mag-fura-2. In permeabilized cells, blockade of the sarco/ER Ca(2+)-ATPase pump in stores partially depleted by IP3 induced further Ca2+ release via an IP3-dependent route, indicating that Ca2+ entry via the sarco/ER Ca(2+)-ATPase pump had been balanced by Ca2+ loss via the IP3-sensitive channel before pump inhibition. IP3-dependent Mn2+ entry, monitored via quenching of luminal mag-fura-2 fluorescence, was readily apparent in filled stores but undetectable in Ca(2+)-depleted stores, indicating markedly reduced IP3-sensitive channel activity in the latter. Also consistent with reduced responsiveness of Ca(2+)-depleted stores to IP3, the initial rate of refilling of these stores was unaffected by the presence of 0.3 microM IP3, a concentration that was clearly effective in eliciting Ca2+ release from filled stores. Analysis of the rate of Ca2+ release at various IP3 concentrations indicated a significant shift of the IP3 dose response toward higher [IP3] with decreasing [Ca2+]s. We conclude that IP3-dependent Ca2+ release in HSY cells is a steady-state process wherein Ca2+ efflux via the IP3 receptor Ca2+ channel is regulated by [Ca2+]s, apparently via changes in the sensitivity of the channel to IP3.

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Ryanodine-induced calcium release from hepatic microsomes and permeabilized hepatocytes

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.268.6.g1017 ◽

1995 ◽

Vol 268 (6) ◽

pp. G1017-G1024 ◽

Cited By ~ 3

Author(s):

L. B. Lilly ◽

J. L. Gollan

Keyword(s):

Polyethylene Glycol ◽

Functional Significance ◽

Calcium Release ◽

Cell Types ◽

Endogenous Ligand ◽

Cell Systems ◽

Permeabilized Cells ◽

Hepatic Microsomes ◽

Inositol 1,4,5 Trisphosphate ◽

Site Of Action

Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] is a second messenger that releases Ca2+ from hepatocyte microsomes. The toxic alkaloid ryanodine modulates Ca2+ release via a receptor (RyR) identified in a variety of cell systems, but its regulation and functional significance in liver are undefined. Similarly, the role in hepatocyte Ca2+ regulation of adenosine 5'-cyclic diphosphate-ribose (cADPR), which is the putative endogenous ligand for RyR in other cell systems, has not been defined. Utilizing microsomes and permeabilized cells, we have investigated Ca2+ regulation in hepatocytes and, in particular, effects of ryanodine, cADPR, and other putative modulators on Ca2+ release and compared these with Ins(1,4,5)P3-induced Ca2+ release. Ryanodine at > or = 50 microM released 20% of microsomal Ca2+, and, in contrast to Ins(1,4,5)P3, no potentiation was observed with guanosine 5'-triphosphate and polyethylene glycol. Ins(1,4,5)P3-induced Ca2+ release was demonstrable after maximal ryanodine-induced Ca2+ release, suggesting that distinct Ca2+ stores are involved. cADPR (5 microM) did not induce Ca2+ release, alone or in combination with calmodulin or hepatic cytosol, nor did it influence ryanodine-induced release, in microsomes or permeabilized hepatocytes (in which ryanodine released 25% of the sequestered Ca2+). Ryanodine-induced Ca2+ release in microsomes was not influenced by 20 mM caffeine, which itself did not mobilize Ca2+, but was prevented by 500 microM tetracaine, which was shown to induce Ca2+ release. We conclude that ryanodine is capable of mobilizing Ca2+ in the hepatocyte from microsomal stores that are distinct from those that can be regulated by Ins(1,4,5)P3 but that cADPR has no such effect. These data suggest that cADPR does not serve as the endogenous ligand for RyR in liver cells or that the site of action of ryanodine in hepatocyte microsomes is distinct from that in other cell types.

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Characterization of the inositol 1,4,5-trisphosphate-induced calcium release from permeabilized endocrine cells and its inhibition by decavanadate and p-hydroxymercuribenzoate

Biochemical Journal ◽

10.1042/bj2620083 ◽

1989 ◽

Vol 262 (1) ◽

pp. 83-89 ◽

Cited By ~ 48

Author(s):

K J Föhr ◽

J Scott ◽

G Ahnert-Hilger ◽

M Gratzl

Keyword(s):

Endocrine Cells ◽

Calcium Release ◽

Cell Types ◽

Inhibitory Effect ◽

Maximal Effect ◽

Thiol Compounds ◽

Inositol 1,4,5 Trisphosphate ◽

Dependent Inhibition ◽

Pheochromocytoma Pc12 ◽

First Time

The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ compartment of endocrine cells was studied with alpha-toxin- and digitonin-permeabilized rat insulinoma (RINA2) and rat pheochromocytoma (PC12) cells. The Ca2+ uptake was ATP-dependent, and submicromolar concentrations of IP3 specifically released the stored Ca2+. Half-maximal Ca2+ release was observed with 0.25-0.5 mumol of IP3/l, and the amount of Ca2+ released due to IP3 could be enhanced by additional loading of the Ca2+ compartment. Consecutive additions of the same concentration of IP3 for 1-2 h always released the same amount of Ca2+ without desensitization, providing an ideal basis to further characterize the IP3-induced Ca2+ release. Here we describe for the first time a reversible inhibitory effect of decavanadate on the IP3-induced Ca2+ release. Among the vanadium species tested (decavanadate, oligovanadate and monovanadate), only decavanadate was inhibitory, with a half-maximal effect at 5 mumol/l in both cell types. The effect of decavanadate could be overcome by increasing the amount of sequestered Ca2+ or added IP3. Decavanadate did not affect the ATP-driven Ca2+ uptake but oligovanadate was inhibitory on Ca2+ uptake. p-Hydroxymercuribenzoate (pHMB) at concentrations between 10 and 30 mumol/l also inhibited the Ca2+ release due to IP3. Thiol compounds such as dithiothreitol (DTT; 1 mmol/l) added before pHMB removed all its inhibitory effect on the IP3-induced Ca2+ release, whereas the inhibition caused by decavanadate was unaffected by DTT. Thus, the decavanadate-dependent inhibition functions by a distinctly different mechanism than pHMB and could serve as a specific tool to analyse various aspects of the IP3-induced Ca2+ release within endocrine cells.

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Kinetics of calcium release mediated by immunoaffinity-purified inositol 1,4,5-trisphosphate receptor (Type I) in reconstituted lipid vesicles

Neuroscience Research Supplements ◽

10.1016/0921-8696(94)92332-9 ◽

1994 ◽

Vol 19 ◽

pp. S26

Author(s):

Junji Hirota ◽

Takayuki Michikawa ◽

Atsushi Miyawaki ◽

Ichiro Okura ◽

Teiichi Furuichi ◽

...

Keyword(s):

Calcium Release ◽

Lipid Vesicles ◽

Receptor Type ◽

Type I ◽

Inositol 1,4,5 Trisphosphate ◽

Trisphosphate Receptor ◽

Kinetics Of

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The Bcl-2 Gene Polymorphism rs956572AA Increases Inositol 1,4,5-Trisphosphate Receptor–Mediated Endoplasmic Reticulum Calcium Release in Subjects with Bipolar Disorder

Biological Psychiatry ◽

10.1016/j.biopsych.2010.10.019 ◽

2011 ◽

Vol 69 (4) ◽

pp. 344-352 ◽

Cited By ~ 48

Author(s):

Rodrigo Machado-Vieira ◽

Natalia B. Pivovarova ◽

Ruslan I. Stanika ◽

Peixiong Yuan ◽

Yun Wang ◽

...

Keyword(s):

Bipolar Disorder ◽

Endoplasmic Reticulum ◽

Gene Polymorphism ◽

Calcium Release ◽

Endoplasmic Reticulum Calcium ◽

Inositol 1,4,5 Trisphosphate ◽

Trisphosphate Receptor

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Partial calcium release in response to submaximal inositol 1,4,5-trisphosphate receptor activation

Molecular and Cellular Endocrinology ◽

10.1016/0303-7207(94)90133-3 ◽

1994 ◽

Vol 98 (2) ◽

pp. 147-156 ◽

Cited By ~ 21

Author(s):

Ludwig Missiaen ◽

Jan B. Parys ◽

Humbert De Smedt ◽

Masahiro Oike ◽

Rik Casteels

Keyword(s):

Calcium Release ◽

Receptor Activation ◽

Inositol 1,4,5 Trisphosphate ◽

Trisphosphate Receptor

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Effect of halothane on intracellular calcium oscillations in porcine tracheal smooth muscle cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1999.276.1.l81 ◽

1999 ◽

Vol 276 (1) ◽

pp. L81-L89 ◽

Cited By ~ 5

Author(s):

Christina M. Pabelick ◽

Y. S. Prakash ◽

Mathur S. Kannan ◽

Keith A. Jones ◽

David O. Warner ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Ryanodine Receptor ◽

Muscle Cells ◽

Calcium Oscillations ◽

Tracheal Smooth Muscle ◽

Permeabilized Cells ◽

Inositol 1,4,5 Trisphosphate ◽

Intracellular Ca ◽

Trisphosphate Receptor

The effect of halothane on intracellular Ca2+ concentration ([Ca2+]i) regulation in porcine tracheal smooth muscle cells was examined with real-time confocal microscopy. Both 1 and 2 minimum alveolar concentration (MAC) halothane increased basal [Ca2+]iwhen Ca2+ influx and efflux were blocked, suggesting increased sarcoplasmic reticulum (SR) Ca2+ leak and/or decreased reuptake. In β-escin-permeabilized cells, heparin inhibition of inositol 1,4,5-trisphosphate-receptor channels blunted the halothane-induced increase in [Ca2+]i. Both 1 and 2 MAC halothane decreased the frequency and amplitude of ACh-induced [Ca2+]ioscillations (which represent SR Ca2+ release through ryanodine-receptor channels), abolishing oscillations in ∼20% of tracheal smooth muscle cells at 2 MAC. When Ca2+ influx and efflux were blocked, halothane increased the baseline and decreased the frequency and amplitude of [Ca2+]ioscillations, inhibiting oscillations in ∼70% of cells at 2 MAC. The fall time of [Ca2+]ioscillations and the rate of fall of the [Ca2+]iresponse to caffeine were both increased by halothane. These results suggest that halothane abolishes agonist-induced [Ca2+]ioscillations by 1) depleting SR Ca2+ via increased Ca2+ leak through inositol 1,4,5-trisphosphate-receptor channels, 2) decreasing Ca2+ release through ryanodine-receptor channels, and 3) inhibiting reuptake.

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Inositol 1,4,5-trisphosphate–induced Calcium Release Is Necessary for Generating the Entire Light Response of Limulus Ventral Photoreceptors

The Journal of General Physiology ◽

10.1085/jgp.200208778 ◽

2003 ◽

Vol 121 (5) ◽

pp. 441-449 ◽

Cited By ~ 8

Author(s):

Alan Fein

Keyword(s):

Calcium Release ◽

Cyclopiazonic Acid ◽

Light Response ◽

Calcium Stores ◽

Ip3 Receptor ◽

Treatment Results ◽

Light Responses ◽

Calcium Buffer ◽

Pressure Injection ◽

Inositol 1,4,5 Trisphosphate

The experiments reported here were designed to answer the question of whether inositol 1,4,5-trisphosphate (IP3)-induced calcium release is necessary for generating the entire light response of Limulus ventral photoreceptors. For this purpose the membrane-permeable IP3 receptor antagonist 2-aminoethoxydiphenyl borate (2APB) (Maruyama, T., T. Kanaji, S. Nakade, T. Kanno, and K. Mikoshiba. 1997. J. Biochem. (Tokyo). 122:498–505) was used. Previously, 2APB was found to inhibit the light activated current of Limulus ventral photoreceptors and reversibly inhibit both light and IP3 induced calcium release as well as the current activated by pressure injection of calcium into the light sensitive lobe of the photoreceptor (Wang, Y., M. Deshpande, and R. Payne. 2002. Cell Calcium. 32:209). In this study 2APB was found to inhibit the response to a flash of light at all light intensities and to inhibit the entire light response to a step of light, that is, both the initial transient and the steady-state components of the response to a step of light were inhibited. The light response in cells injected with the calcium buffer 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) was reversibly inhibited by 2APB, indicating that these light responses result from IP3-mediated calcium release giving rise to an increase in Cai. The light response obtained from cells after treatment with 100 μM cyclopiazonic acid (CPA), which acts to empty intracellular calcium stores, was reversibly inhibited by 2APB, indicating that the light response after CPA treatment results from IP3-mediated calcium release and a consequent rise in Cai. Together these findings imply that IP3-induced calcium release is necessary for generating the entire light response of Limulus ventral photoreceptors.

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Luminal calcium regulation of calcium release from sarcoplasmic reticulum

Bioscience Reports ◽

10.1007/bf01788370 ◽

1995 ◽

Vol 15 (5) ◽

pp. 387-397 ◽

Cited By ~ 19

Author(s):

Cecilia Hidalgo ◽

Paulina Donoso

Keyword(s):

Sarcoplasmic Reticulum ◽

Calcium Concentration ◽

Calcium Release ◽

Single Channel ◽

Release Rates ◽

Calcium Release Channels ◽

Channel Opening ◽

Inositol 1,4,5 Trisphosphate ◽

Luminal Calcium ◽

Trisphosphate Receptor

This article discusses how changes in luminal calcium concentration affect calcium release rates from triad-enriched sarcoplasmic reticulum vesicles, as well as single channel opening probability of the ryanodine receptor/calcium release channels incorporated in bilayers. The possible participation of calsequestrin, or of other luminal proteins of sarcoplasmic reticulum in this regulation is addressed. A comparison with the regulation by luminal calcium of calcium release mediated by the inositol 1,4,5-trisphosphate receptor/calcium channel is presented as well.

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