Mid-range calcium signaling favors activation of Ca2+-activated Cl- channels through functional coupling between SOCE, SERCA and IP3 receptors

We present here evidence for the enhancement, at rest, of an inositol 1,4,5-trisphosphate (IP3)–mediated calcium signaling pathway in myotubes from dystrophin-deficient cell lines (SolC1(−)) as compared to a cell line from the same origin but transfected with mini-dystrophin (SolD(+)). With confocal microscopy, the number of sites discharging calcium (release site density [RSD]) was quantified and found more elevated in SolC1(−) than in SolD(+) myotubes. Variations of membrane potential had no significant effect on this difference, and higher resting [Ca2+]i in SolC1(−) (Marchand, E., B. Constantin, H. Balghi, M.C. Claudepierre, A. Cantereau, C. Magaud, A. Mouzou, G. Raymond, S. Braun, and C. Cognard. 2004. Exp. Cell Res. 297:363–379) cannot explain alone higher RSD. The exposure with SR Ca2+ channel inhibitors (ryanodine and 2-APB) and phospholipase C inhibitor (U73122) significantly reduced RSD in both cell types but with a stronger effect in dystrophin-deficient SolC1(−) myotubes. Immunocytochemistry allowed us to localize ryanodine receptors (RyRs) as well as IP3 receptors (IP3Rs), IP3R-1 and IP3R-2 isoforms, indicating the presence of both RyRs-dependent and IP3-dependent release systems in both cells. We previously reported evidence for the enhancement, through a Gi protein, of the IP3-mediated calcium signaling pathway in SolC1(−) as compared to SolD(+) myotubes during a high K+ stimulation (Balghi, H., S. Sebille, B. Constantin, S. Patri, V. Thoreau, L. Mondin, E. Mok, A. Kitzis, G. Raymond, and C. Cognard. 2006. J. Gen. Physiol. 127:171–182). Here we show that, at rest, these regulation mechanisms are also involved in the modulation of calcium release activities. The enhancement of resting release activity may participate in the calcium overload observed in dystrophin-deficient myotubes, and our findings support the hypothesis of the regulatory role of mini-dystrophin on intracellular signaling.

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Functional Coupling between mGluR1 and Cav3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines

Journal of Neuroscience ◽

10.1523/jneurosci.0362-09.2009 ◽

2009 ◽

Vol 29 (31) ◽

pp. 9668-9682 ◽

Cited By ~ 62

Author(s):

M. E. Hildebrand ◽

P. Isope ◽

T. Miyazaki ◽

T. Nakaya ◽

E. Garcia ◽

...

Keyword(s):

Calcium Channels ◽

Purkinje Cell ◽

Calcium Signaling ◽

Dendritic Spines ◽

Parallel Fiber ◽

Functional Coupling

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Negative modulation of inositol 1,4,5-trisphosphate type 1 receptor expression prevents dystrophin-deficient muscle cells death

AJP Cell Physiology ◽

10.1152/ajpcell.00048.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. C1133-C1145 ◽

Cited By ~ 14

Author(s):

Ludivine Mondin ◽

Haouaria Balghi ◽

Bruno Constantin ◽

Christian Cognard ◽

Stéphane Sebille

Keyword(s):

Cell Death ◽

Calcium Signaling ◽

Calcium Release ◽

Receptor Expression ◽

Type I ◽

Ip3 Receptors ◽

Inositol 1,4,5 Trisphosphate ◽

Interesting Approach ◽

Long Time ◽

Short Time

Evidence for a modulatory effect of cyclosporin A (CsA) on calcium signaling and cell survival in dystrophin-deficient cells is presented. Our previous works strongly supported the hypothesis of an overactivation of Ca2+ release via inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) in dystrophin-deficient cells, both during membrane depolarization and at rest, through spontaneous Ca2+ release events. Forced expression of mini-dystrophin in these cells contributed, during stimulation and in resting condition, to the recovery of a controlled calcium homeostasis. In the present work, we demonstrate that CsA exposure displayed a dual-modulator effect on calcium signaling in dystrophin-deficient cells. Short-time incubation induced a decrease of IP3-dependent calcium release, leading to patterns of release similar to those observed in myotubes expressing mini-dystrophin, whereas long-time incubation reduced the expression of the type I of IP3 receptors (IP3R-1) RNA levels. Moreover, both IP3R-1 knockdown and blockade through 2-aminoethoxydiphenyle borate or CsA induced improved survival of dystrophin-deficient myotubes, demonstrating the cell death dependence on the IP3-dependent calcium signaling as well as the protective effect of CsA. Inhibition of the IP3 pathway could be a very interesting approach for reducing the natural cell death of dystrophin-deficient cells in development.

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Functional coupling between the caffeine/ryanodine-sensitive Ca2+ store and mitochondria in rat aortic smooth muscle cells

Biochemical Journal ◽

10.1042/bj3570363 ◽

2001 ◽

Vol 357 (2) ◽

pp. 363-371 ◽

Cited By ~ 12

Author(s):

Olivier VALLOT ◽

Laurent COMBETTES ◽

Anne-Marie LOMPRÉ

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Muscle Cells ◽

Mitochondrial Activity ◽

Functional Coupling ◽

Ip3 Receptors ◽

Aortic Smooth Muscle Cells ◽

Aortic Smooth Muscle

We investigated the role of mitochondria in the agonist-induced and/or caffeine-induced Ca2+ transients in rat aortic smooth muscle cells. We explored the possibility that proliferation modulates the coupling between mitochondria and endoplasmic reticulum. Ca2+ transients induced by either ATP or caffeine were measured in presence or absence of drugs interfering with mitochondrial activity in freshly dissociated cells (day 1) and in subconfluent primary culture (day 12). We found that the mitochondrial inhibitors, rotenone or carbonyl cyanide m-chlorophenylhydrazone, as well as the permeability transition pore inhibitor, cyclosporin A, had no effect on the ATP-induced Ca2+ transient at either day 1 or day 12, but prevented caffeine-induced cytosolic Ca2+ increase at day 12 but not at day 1. Close connections between ryanodine receptors and mitochondria were observed at both day 1 and 12. Thapsigargin (TG) prevented ATP- and caffeine-induced Ca2+ transients at day 1. At day 12, where only 50% of the cells were sensitive to caffeine, TG did not prevent the caffeine-induced Ca2+ transient, and prevented ATP-induced Ca2+ transient in only half of the cells. Together, these data demonstrate that rat aortic smooth muscle cells at day 1have an ATP- and caffeine-sensitive pool, which is functionally independent but physically closely linked to mitochondria and totally inhibited by TG. At day 12, we propose the existence of two cell populations: half contains IP3 receptors and TG-sensitive Ca2+ pumps only; the other half contains, in addition to the IP3-sensitive pool independent from mitochondria, a caffeine-sensitive pool. This latter pool is linked to mitochondria through the permeability transition pore and is refilled by both TG-sensitive and insensitive mechanisms.

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Functional Coupling of Chromogranin with the Inositol 1,4,5-Trisphosphate Receptor Shapes Calcium Signaling

Journal of Biological Chemistry ◽

10.1074/jbc.m311261200 ◽

2004 ◽

Vol 279 (34) ◽

pp. 35551-35556 ◽

Cited By ~ 26

Author(s):

Chi-Un Choe ◽

Kenneth D. Harrison ◽

Wayne Grant ◽

Barbara E. Ehrlich

Keyword(s):

Calcium Signaling ◽

Functional Coupling ◽

Inositol 1,4,5 Trisphosphate ◽

Trisphosphate Receptor

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New Aspects of Cytosloic Calcium Signaling

Physiology ◽

10.1152/physiologyonline.1996.11.1.13 ◽

1996 ◽

Vol 11 (1) ◽

pp. 13-17 ◽

Cited By ~ 3

Author(s):

OH Petersen

Keyword(s):

Endoplasmic Reticulum ◽

Simple Model ◽

Calcium Signaling ◽

Inositol Trisphosphate ◽

Ip3 Receptors ◽

Messenger System ◽

Intracellular Messenger

Hormone- or neurotransmitter-evoked cytosolic Ca2+ signals are generally thought to be initiated by an increase in inositol trisphosphate (IP3) concentration that in turn opens Ca2+ release channels in the endoplasmic reticulum. Recent data challenge this simple model and indicate IP3 receptors in several organelles and an additional intracellular messenger system for Ca2+ regulation.

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