I ARC, a Novel Arachidonate-regulated, Noncapacitative Ca2+ Entry Channel

Mignen, Olivier; Shuttleworth, Trevor J.

doi:10.1074/jbc.275.13.9114

Cited by 184 publications

(215 citation statements)

References 30 publications

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“…As such, they operate within a relatively rapid time frame, typically of less than a second, and inactivation is directly related to the amount of Ca 2ϩ current through the channel. Such fast inactivation by permeating Ca 2ϩ ions is not seen in currents through ARC channels (10). Moreover, the Ca 2ϩ -dependent inhibition described for ARC channels is still observed in divalent-free external media, when the channels are conducting monovalent cations (13).…”

Section: Methodsmentioning

confidence: 99%

“…Electrophysiological Recordings-Patch-clamp recordings of macroscopic whole-cell currents were performed using an Axopatch-1C patchclamp amplifier (Axon Instruments, Foster City, CA) as previously described (10). The standard pipette (internal) solution contained (mM): cesium acetate 140, NaCl 10, MgCl 2 1.22, EGTA 5, HEPES 10 (pH 7.2) unless otherwise specified.…”

Section: Methodsmentioning

confidence: 99%

“…Most relevant was the question of whether calcineurin activity also influenced currents through the endogenous store-operated Ca 2ϩ -selective (SOC) currents in the m3-HEK cells (10). These currents display most of the characteristic features of the classic CRAC channels first described in mast cells and Jurkat lymphocytes (24,25).…”

Section: Calcineurin and The Regulation Of Ca 2ϩ Entry 40089mentioning

confidence: 99%

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Calcineurin Directs the Reciprocal Regulation of Calcium Entry Pathways in Nonexcitable Cells

Mignen

Thompson

Shuttleworth

2003

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Calcineurin and The Regulation Of Ca 2ϩ Entry 40089mentioning

confidence: 99%

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Calcineurin Directs the Reciprocal Regulation of Calcium Entry Pathways in Nonexcitable Cells

Mignen

Thompson

Shuttleworth

2003

Journal of Biological Chemistry

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“…They were imaged on a TILL Photonics system with a monochromator (TILL Photonics, Planegg, Germany) and a progressive line-scan digital camera (Imago, Scientific Instruments, Madison, WI). The cells were stimulated with 0.5 M carbamylcholine (CCh) to induce Ca 2ϩ oscillations, then 1 mM La 3ϩ was added to block both Ca 2ϩ entry and the plasma membrane Ca 2ϩ pump (29)(30)(31)(32)(33). Fig.…”

Section: Experimental Verificationmentioning

confidence: 99%

Control of calcium oscillations by membrane fluxes

Sneyd

Tsaneva-Atanasova

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

126

116

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It is known that Ca 2؉ influx plays an important role in the modulation of inositol trisphosphate-generated Ca 2؉ oscillations, but controversy over the mechanisms underlying these effects exists. In addition, the effects of blocking membrane transport or reducing Ca 2؉ entry vary from one cell type to another; in some cell types oscillations persist in the absence of Ca 2؉ entry (although their frequency is affected), whereas in other cell types oscillations depend on Ca 2؉ entry. We present theoretical and experimental evidence that membrane transport can control oscillations by controlling the total amount of Ca 2؉ in the cell (the Ca 2؉ load). Our model predicts that the cell can be balanced at a point where small changes in the Ca 2؉ load can move the cell into or out of oscillatory regions, resulting in the appearance or disappearance of oscillations. Our theoretical predictions are verified by experimental results from HEK293 cells. We predict that the role of Ca 2؉ influx during an oscillation is to replenish the Ca 2؉ load of the cell. Despite this prediction, even during the peak of an oscillation the cell or the endoplasmic reticulum may not be measurably depleted of Ca 2؉ .I n response to an increased concentration of inositol trisphosphate (IP 3 ), oscillations in the concentration of free intracellular calcium (Ca 2ϩ ) occur in many cell types and are important for the control of many cellular functions (1-4). In nonexcitable cells, such as epithelial cells, these oscillations occur as the result of Ca 2ϩ flux into and out of the endoplasmic reticulum (ER). However, although the oscillations result from the cycling of Ca 2ϩ between the ER and the cytoplasm, the transport of Ca 2ϩ across the cell membrane can have a dramatic effect on these oscillations.Although Ca 2ϩ influx is known to be important, disagreement exists, first, over the mechanisms by which Ca 2ϩ influx is modulated during a Ca 2ϩ oscillation, and, second, over the role played by Ca 2ϩ influx. The capacitative entry hypothesis proposes that depletion of ER Ca 2ϩ causes enhanced entry of Ca 2ϩ across the plasma membrane (5-9). Often, although not necessarily, in this scenario, Ca 2ϩ entry is necessary for the refilling of the ER, and thus oscillation frequency is controlled by the refilling time (10, 11). Although capacitative entry is certainly an important factor during the response to a maximal stimulus, other investigators have pointed to a lack of direct evidence that it plays an important role during smaller stimuli that generate oscillatory behavior (12). They maintain that Ca 2ϩ influx, under these conditions, is controlled by a noncapacitative pathway involving arachidonic acid and that the purpose of the influx is to increase the likelihood that low levels of IP 3 will induce Ca 2ϩ release from internal stores (13). This controversy is complicated by the fact that, in some cell types, Ca 2ϩ oscillations persist in the absence of Ca 2ϩ influx (14-16), whereas in other cell types, oscillations depend absolutely on influx (17, ...

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“…17 and 18). In the HEK293 cell line, capacitative and noncapacitative pathways co-exist (19,20). In these cells, muscarinic receptor activation can lead to baseline [Ca 2ϩ ] i spikes or [Ca 2ϩ ] i oscillations.…”

mentioning

confidence: 99%

Mutual Antagonism of Calcium Entry by Capacitative and Arachidonic Acid-mediated Calcium Entry Pathways

Luo¹,

Broad²,

Bird

et al. 2001

Journal of Biological Chemistry

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In nonexcitable cells, the predominant mechanism for regulated entry of Ca 2؉ is capacitative calcium entry, whereby depletion of intracellular Ca 2؉ stores signals the activation of plasma membrane calcium channels. A number of other regulated Ca 2؉ entry pathways occur in specific cell types, however, and it is not know to what degree the different pathways interact when present in the same cell. In this study, we have examined the interaction between capacitative calcium entry and arachidonic acid-activated calcium entry, which co-exist in HEK293 cells. These two pathways exhibit mutual antagonism. That is, capacitative calcium entry is potently inhibited by arachidonic acid, and arachidonic acid-activated entry is inhibited by the pre-activation of capacitative calcium entry with thapsigargin. In the latter case, the inhibition does not seem to result from a direct action of thapsigargin, inhibition of endoplasmic reticulum Ca 2؉ pumps, depletion of Ca 2؉ stores, or entry of Ca 2؉ through capacitative calcium entry channels. Rather, it seems that a discrete step in the pathway signaling capacitative calcium entry interacts with and inhibits the arachidonic acid pathway. The findings reveal a novel process of mutual antagonism between two distinct calcium entry pathways. This mutual antagonism may provide an important protective mechanism for the cell, guarding against toxic Ca 2؉ overload.

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I ARC, a Novel Arachidonate-regulated, Noncapacitative Ca2+ Entry Channel

Abstract: The prevailing model of receptor-activated Ca 2ϩ entry in non-excitable cells is the so-called "capacitative" or store-operated model in which the emptying of the agonist-sensitive stores alone is both necessary and sufficient to activate Ca 2ϩ

Cited by 184 publications

References 30 publications

Calcineurin Directs the Reciprocal Regulation of Calcium Entry Pathways in Nonexcitable Cells

Calcineurin Directs the Reciprocal Regulation of Calcium Entry Pathways in Nonexcitable Cells

Control of calcium oscillations by membrane fluxes

Mutual Antagonism of Calcium Entry by Capacitative and Arachidonic Acid-mediated Calcium Entry Pathways

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