Department of Physiology, Loyola University Chicago, Maywood, Illinois
Submitted 3 June 2005 ; accepted in final form 3 August 2005
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Ca2+/calmodulin-dependent kinase II; calcium regulation; capacitative calcium entry
The sustained phase of the Ca2+ response to agonist stimulation is carried by CCE resulting from ER Ca2+ store depletion. In VECs, CCE leads to replenishing of intracellular Ca2+ stores; activates important second messengers, including nitric oxide (NO) release (10); and plays a role in cell volume regulation and cell proliferation (5). Although CCE has been demonstrated in various cell types, the underlying molecular mechanisms of its activation and regulation are still elusive in many aspects (19, 40). Several signaling pathways have been proposed for the regulation of CCE, including conformational coupling between ER and surface membrane ion channel proteins or an ER resident generation of a diffusible Ca2+ influx factor (CIF). CIF diffuses to the plasma membrane to activate CCE through store-operated Ca2+ channels and appears to require protein phosphorylation to maintain its activity (37). Several protein kinases, including tyrosine kinase (44), protein kinase C (1), and myosin light-chain kinase (MLCK) (51), have been implicated as playing important roles in the regulation of CCE. CaMKII has been shown to regulate ion channels that may be involved in CCE. In chick skeletal muscle cells, inhibitors of CaM (trifluoperazine) and CaMKII {1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62)} completely abolished store-operated Ca2+ influx (52). Similarly, in thyroid FRTL-5 cells (Fischer rat thyroid line 5), KN-62 inhibited Ca2+ entry after ATP- and thapsigargin-dependent Ca2+ store depletion (50).
Having established previously that Ca2+/CaM plays crucial roles in NO production and CCE regulation in calf pulmonary artery endothelial (CPAE) cells (10, 42), in the present study, we have focused specifically on the elucidation of the role of CaMKII in the complex interplay between agonist-induced intracellular Ca2+ release, Ca2+ store depletion, and activation of CCE in this cell type. We found that various inhibitors of CaMKII altered the time course of ATP-induced [Ca2+]i transients, primarily by reducing its sustained component, thus inhibiting CCE. CaMKII inhibitors themselves, however, were also able to cause intracellular Ca2+ release, presumably from an IP3-dependent Ca2+ store. The data suggest that CaMKII activity plays an important regulatory role for both Ca2+ release and CCE. A previous account of this work was presented previously in abstract form (2).
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Measurement of [Ca2+]i. Spatially averaged [Ca2+]i measurements from single CPAE cells were performed using the ratiometric Ca2+ indicator indo-1. Cells were loaded by exposure to 1 ml of standard Tyrode solution containing 5 µM indo-1 acetoxymethyl ester (indo-1 AM; Molecular Probes, Eugene, OR) and 5 µl of a Pluronic F-127 stock solution (0.2 g/ml Pluronic F-127 dissolved in DMSO) for 20 min at room temperature. [Ca2+]i was measured by exciting indo-1 fluorescence with light emission of 360-nm wavelength and measuring emitted fluorescence signals simultaneously at 405 nm (F405) and 485 nm (F485). Single-cell fluorescence signals were recorded using photomultiplier tubes (model R2693; Hamamatsu, Bridgewater, NJ), and changes in [Ca2+]i are expressed as changes of the ratio R = F405/F485.
Solutions and chemicals. Cells were superfused with standard Tyrode solution that contained (in mM) 135 NaCl, 4 KCl, 1 MgCl2, 2 CaCl2, 10 glucose, and 10 HEPES, with pH adjusted to 7.3 using NaOH. In Ca2+-free Tyrode solution, CaCl2 was omitted (i.e., nominally Ca2+-free solution). ATP (Na+ salt) and 2-aminoethoxydiphenyl borate (2-APB) were obtained from Sigma (St. Louis, MO); [N-(2-hydroxyethyl)-N-(4-methoxybenzenesulfonyl)] amino-N-(4-chlorocinnamyl)-N-methyl benzylamine (KN-93), 1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62), and autocamtide-2-related inhibitory peptide (AIP) were purchased from Calbiochem (San Diego, CA); and thapsigargin was obtained from Alexis (San Diego, CA). ATP, KN-93, and AIP were dissolved in distilled water. KN-62 (10 mM), thapsigargin (10 mM), and 2-APB (20 mM) were dissolved in DMSO and diluted to the final indicated concentrations in normal Tyrode solution. All reagents were prepared on the day of experimentation.
Measurement of Mn2+ influx. Mn2+ was used as a substitute for Ca2+ to characterize unidirectional ion flux through the CCE pathway. Intracellularly, Mn2+ binds to indo-1 and quenches its fluorescence. The rate of Mn2+ entry (1 mM [Mn2+]o) was established previously (43); therefore, CCE activity was inferred from the rate of quenching (dF424/dt) of indo-1 fluorescence excited at 360 nm and measured at the Ca2+-independent emission wavelength of 424 nm (F424; the Ca2+-isosbestic, Mn2+-sensitive emission wavelength).
Data analysis. Data are reported as means ± SE for the indicated number (n) of cells. Each experiment was performed on a separate coverslip. Statistical differences among the data were determined using Student's t-test for paired and unpaired data, and data were considered significant at P < 0.05.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
We examined the effect of two other highly potent and specific CaMKII blockers with different structures or modes of action. Both blockers were applied together with ATP. The structurally unrelated KN-62 (50 µM, Fig. 2A), which acts by a mechanism similar to that of KN-93, reduced the average R of the sustained phase from 0.82 ± 0.06 (n = 50) to 0.36 ± 0.14 (n = 6). AIP (20 µM), a nonphosphorylatable, competitive substrate for autophosphorylation of CaMKII resulted in a similar effect. The average
R of the sustained phase of the [Ca2+]i transient was only 0.32 ± 0.09 (n = 10) in the presence of AIP. Similarly to KN-93, KN-62 and AIP had little effect on the peak of the [Ca2+]i transient.
|
|
|
On the basis of the knowledge that the peak phase of the ATP-induced [Ca2+]i transient results predominately from Ca2+ release from internal stores, whereas the sustained plateau phase results from Ca2+ entry via CCE, the data presented thus far suggest that CaMKII inhibitors are capable of releasing Ca2+ but also had a pronounced inhibitory effect on CCE. The following experiments were designed to test the hypothesis that 1) inhibition of CaMKII activity can indeed release Ca2+ from ER Ca2+ stores and 2) CaMKII is an important contributor to the activation of CCE.
ATP- and KN-93-induced [Ca2+]i transients in the absence of extracellular Ca2+.
To examine the effects of CaMKII inhibitors exclusively on Ca2+ release from internal stores, ATP and KN-93 were applied to CPAE cells in the absence of extracellular Ca2+. Figure 5A shows an example of a control [Ca2+]i transient evoked by bath application of ATP (5 µM) in Ca2+-free external solution. The ATP-induced [Ca2+]i transient was characterized by a rapid and pronounced initial rise in [Ca2+]i, which then declined completely to the prestimulatory level even in the maintained presence of extracellular ATP. When ATP was applied simultaneously with KN-93, a [Ca2+]i transient of similar amplitude was observed (Fig. 5B). On average (Fig. 5D), the amplitude of the [Ca2+]i transient evoked by ATP was R = 1.40 ± 0.08 (n = 53). The amplitude evoked with ATP plus KN-93 was
R = 1.50 ± 0.14 (n = 13). The average amplitude was
R = 1.24 ± 0.09 (n = 31) when KN-93 was applied alone (Fig. 5C). Even though these average amplitudes were not significantly different (P > 0.05), they suggest that the action of ATP and KN-93 was slightly additive. However, the rate of decay was different. In the presence of KN-93, the decline of the [Ca2+]i transient was accelerated. This difference in the rates of decline suggests that KN-93 accelerated Ca2+ sequestration, possibly by enhancing the refilling of ER Ca2+ stores. The CaMKII inhibitor AIP (20 µM; data not shown) was also capable of triggering a [Ca2+]i transient similar to that triggered by KN-93, suggesting that the [Ca2+]i transients were the result of inhibition of CaMKII and not due to an unspecific effect of the inhibitors.
|
Intracellular Ca2+ source for KN-93-induced Ca2+ response.
The data presented in Fig. 5C clearly indicated that the CaMKII inhibitor KN-93 caused substantial release of Ca2+. We tested whether KN-93 and ATP increased [Ca2+]i by mobilizing Ca2+ from the same IP3-sensitive intracellular Ca2+ store (10, 28). As shown in Fig. 6A, repetitive, brief KN-93 applications (100 µM, 10 s; n = 3 cells) in Ca2+-free conditions evoked [Ca2+]i transients with progressively decreasing amplitudes due to store depletion. Subsequent application of ATP induced only a small increase in [Ca2+]i. In three separate experiments, the subsequent application of ATP to KN-93-treated cells induced a Ca2+ response that had a mean peak amplitude of R = 0.12 ± 0.04; i.e., <10% of typical [Ca2+]i transient amplitude. This suggests that repetitive stimulation with KN-93 had depleted the same Ca2+ store from which stimulation with ATP releases Ca2+. Alternatively, after repetitive ATP application (5 µM, 10-s applications), subsequent exposure to KN-93 failed to increase [Ca2+]i (n = 5) (Fig. 6B). The data indicate that ATP and KN-93 induced Ca2+ release from a common intracellular Ca2+ store.
|
Effect of inhibition of IP3 receptor on ATP- and KN-93-induced Ca2+ response. It was shown previously (20, 28) that in CPAE cells, the pathway that links the surface membrane purinoceptors to intracellular Ca2+ release involves the IP3 signaling cascade. Therefore, we investigated whether the KN-93-induced increase in [Ca2+]i involved IP3-dependent Ca2+ release. For these experiments, we used the membrane-permeant IP3R blocker 2-aminoethoxydiphenyl borate (2-APB) (27, 29, 59). Figure 7A shows repetitive stimulation with ATP (5 µM) in Ca2+-free conditions. Between exposures to ATP, cells were placed in 2 mM [Ca2+]o for 20 min to allow the Ca2+ stores to fully reload (10). Repetitive exposure to ATP caused reproducible [Ca2+]i transients of virtually identical magnitude and kinetics. Exposure to 2-APB (20 µM) 10 min before the third stimulation with ATP led to a significant reduction of the amplitude of the ATP-induced [Ca2+]i transient (Fig. 7C). On average, the [Ca2+]i transient was reduced by 64 ± 6% (P < 0.05). These results confirm prior observations that the ATP-induced [Ca2+]i transient is due to Ca2+ release through IP3Rs (24, 32, 35, 36, 39, 46). Using the same protocol, we investigated the potential role of IP3Rs for mediating the effect of KN-93 on [Ca2+]i. Figure 7B shows control [Ca2+]i transients with similar amplitudes induced by two subsequent exposures to KN-93 (50 µM). Incubation with 20 µM [2-APB] for 10 min before the third stimulation with KN-93 also resulted in a significant inhibition of the KN-93-induced [Ca2+]i transient (Fig. 7C). On average, the [Ca2+]i transient amplitude was reduced by 91 ± 6% (P < 0.05). Thus the significant inhibition of the KN-93 induced [Ca2+]i transient by 2-APB indicated that KN-93 caused IP3-dependent Ca2+ release.
|
In Fig. 8A, store depletion was achieved by prolonged exposure to 5 µM ATP (see Ref. 43) in Ca2+-free external solution, which elicited a [Ca2+]i transient due to mobilization of Ca2+ from intracellular stores. After recovery of the ATP-induced [Ca2+]i transient readmission of 2 mM [Ca2+]o generated a second elevation of [Ca2+]i, which was identified previously as CCE transient (10, 18, 25, 42). The combined application of ATP and KN-93 (50 µM) in the absence of extracellular Ca2+ (Fig. 8B) caused a robust [Ca2+]i transient of similar magnitude. Subsequent exposure to 2 mM [Ca2+]o (in the maintained presence of KN-93), however, failed to elicit a pronounced CCE transient. As shown in Fig. 8C, KN-93 reduced the amplitude of the CCE transient from R = 0.44 ± 0.05 (control; n = 22) to 0.17 ± 0.06 (n = 7; P < 0.05), or by 61%. These results confirmed that KN-93 exerted a profound inhibitory effect on CCE, presumably through inhibition of CaMKII.
|
|
Finally, we studied the effect of KN-93 on CCE with a third experimental protocol that allowed us to monitor the rate of CCE in CPAE cells directly (see Ref. 25). Mn2+ influx after depletion of intracellular stores with thapsigargin was measured. Mn2+ ions enter cells through the CCE pathway. Mn2+ entry can be used to estimate CCE activity from the rate of quenching of indo-1 fluorescence measured at a Ca2+-insensitive emission wavelength (424 nm). As shown in Fig. 10A, the rate of quenching of the indo-1 signal increased after exposure of thapsigargin-treated cells to Mn2+. However, the addition of KN-93 (50 µM) during Mn2+ influx slowed the indo-1 quenching rate, suggesting inhibition of CCE. In a total of 10 cells, the rate (expressed as the change in indo-1 fluorescence with time, dF/dt) of Mn2+ entry was significantly reduced by 82 ± 6% (P < 0.05) (Fig. 10B) compared with the rate of quenching in the absence of KN-93. Taken together, our results show that a Ca2+/Mn2+-permeable plasma membrane channel activated after store depletion (and therefore CCE) is a target for an inhibitory effect of KN-93 in CPAE cells, suggesting that CaMKII plays a role in the activation of CCE.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
CaMKII and intracellular Ca2+ release.
There are several potential mechanisms through which CaMKII can affect Ca2+ release from IP3-sensitive Ca2+ stores. The prime candidate of modulation of IP3-dependent Ca2+ release is protein phosphorylation by CaMKII. Earlier studies have suggested that CaMKII can phosphorylate the IP3R (12, 58); however, these reports on the effect of IP3R phosphorylation for Ca2+ release and IP3R activity are contradictory, because both inhibition (30, 45, 58) and enhancement (9, 11, 48, 53) of Ca2+ release and/or IP3R channel activity have been observed. A recent study (3), however, has shed new light on the effect of IP3R phosphorylation by CaMKII. Bare et al. (3) showed that CaMKII phosphorylates IP3R type-2 (IP3R type 2 is also the predominant isoform in CPAE cells; unpublished results by J. R. Holda, G. A. Mignery, and L. A. Blatter) and incorporation of CaMKII-treated IP3Rs into planar lipid bilayers revealed that the IP3R-mediated channel open probability was reduced >10-fold by phosphorylation via CaMKII. The study presents strong evidence that the IP3R and CaMKII are two central components of a multiprotein signaling complex. The strong inhibition of IP3R channel activity by CaMKII phosphorylation is compatible with the suggestion that in CPAE cells, tonic activity of CaMKII inhibits IP3Rs and inhibition of CaMKII allows basal IP3 levels to cause Ca2+ release. Our observations are similar to the results obtained in rat pulmonary artery endothelial cells (34), in which inhibition of MLCK has been demonstrated to release Ca2+ from an IP3R-controlled Ca2+ store.
While this possibility of regulation of IP3R activity through tonic inhibition is intriguing, other actions of CaMKII affect IP3R-mediated Ca2+ release. CaMKII has been suggested to modulate IP3 metabolism by regulating two key enzymes involved in IP3 breakdown: Ins(1,4,5)P3 3-kinase (7) and Ins(1,4,5)P3 5-phosphatase (8). Therefore, changes in CaMKII activity affect IP3 levels directly. Particularly, the phosphorylation of Ins(1,4,5)P3 3-kinase by CaMKII enhances its activity and accelerates the breakdown of IP3. Inhibition of CaMKII in turn is expected to cause an increase in cytosolic IP3 levels that may be sufficient to result in the activation of Ca2+ release. This putative mechanism might be reinforced by altered levels of Ins(1,3,4,5)P4, a product of Ins(1,4,5)P3 3-kinase action and its effect on Ca2+ release (16, 21).
In addition, the possibility must be considered that the CaMKII inhibitor KN-93 may modulate Ca2+ release through a CaMKII-independent mechanism. KN-93 inhibits CaMKII by preventing CaM binding to the enzyme and therefore could interfere with any potential CaM binding site. For example, CaM inhibits PLC (41) and therefore decreases IP3 production. KN-93 binding to PLC could therefore reverse this inhibitory action of CaM and lead to increased IP3 production (31). Furthermore, through a similar mechanism, KN-93 could prevent inhibition of the IP3R by CaM (49). Nonetheless, it seems unlikely that the effects of KN-93 in our present study occurred solely through a CaMKII-independent pathway, because we observed the same effects with the antagonist AIP, which acts through a completely different mechanism. (AIP binds to the substrate-binding site and not to the CaM-binding site of the kinase.) Furthermore, all CaMKII inhibitors were applied in a concentration range that is considered to cause specific and selective inhibition of CaMKII. The effective inhibitory concentration values of [KN-62] and [KN-93] have been determined to be 1 µM (17) and 20 µM (22), respectively, with no significant effect observed at concentrations 100 µM on activities of other kinases, such as MLCK, PKC, or cAMP-dependent protein kinase II. At micromolar concentrations, AIP is also a highly selective inhibitor of CaMKII and the concentration used (20 µM) has little effect on the activities of PKA, PKC, and CaMKIV (22). Therefore, the concentrations of inhibitors used in the present study were in the range expected to produce selective inhibition of CaMKII.
CaMKII and CCE.
In addition to Ca2+ release, CaMKII inhibitors caused inhibition of CCE independently of whether CCE was activated after store depletion in response to stimulation with ATP (Fig. 1B) or thapsigargin (Fig. 6A). This finding suggests a point of action by CaMKII in the regulation of the CCE activation signal transduction cascade that is common for receptor-dependent or receptor-independent store depletion. The similar effects on CCE of KN-93, KN-62, and AIP provide additional evidence for a specific role for CaMKII in this process. CaMKII activity has been associated with CCE activation in other cell types, including Chinese hamster ovary cells (14) and Xenopus oocytes (26).
Several mechanisms can be envisioned through which CaMKII can enhance CCE activity. Several protein kinases, including tyrosine kinases (TKs) and MLCK, have been shown to be involved in CCE regulation in endothelial cells (13, 34, 47, 56, 57), and it has become increasingly clear that phosphorylation is involved in the activation of CCE (4, 15, 23, 54). Thus a likely explanation of the mechanism of the effect CaMKII inhibitors on CCE would involve phosphorylation of the CCE channel (or a regulatory protein of the CCE pathway) by CaMKII. The CCE pathway may have even more than one phosphorylation site that would allow for finely tuned regulation by a variety of different kinases, including TKs, MLCK, and CaMKII.
An additional target for CaMKII-dependent regulation may be the signaling cascade linking store depletion to activation of the Ca2+ entry pathway. Although the molecular identity of the underlying mechanism remains elusive, several models have been proposed (for review, see Ref. 19), including conformational coupling of release and entry channel proteins, ER-dependent generation of a soluble cytoplasmic messenger (CIF), and store depletion-activated CCE channel insertion. CIF has been shown to require phosphorylation to maintain activity (37) in which CaMKII could play a role. Although to date there is no evidence for CIF in VECs, this mechanism cannot be ruled out on the basis of the findings of our present study.
Conclusion.
We have demonstrated that CaMKII inhibitors cause the release of Ca2+ from intracellular stores and inhibit CCE. Taken together, we conclude that CaMKII plays an important role in the regulation of intracellular Ca2+ release and the subsequent activation of CCE in VECs, presumably through phosphorylation of two important Ca2+-handling proteins: the IP3 receptor Ca2+ release channel and the CCE membrane channel. Both actions of CaMKII have in common that they favor refilling the ER with Ca2+.
![]() |
GRANTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
ACKNOWLEDGMENTS |
---|
![]() |
FOOTNOTES |
---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2. Aromolaran AS and Blatter LA. Effects of Ca2+/calmodulin-dependent protein kinase II inhibitors on Ca2+ signaling in bovine vascular endothelial cells. Biophys J 84: 392a, 2003.
3. Bare DJ, Kettlun CS, Liang M, Bers DM, and Mignery GA. Cardiac type 2 inositol 1,4,5-trisphosphate receptor: interaction and modulation by calcium/calmodulin-dependent protein kinase II. J Biol Chem 280: 1591215920, 2005.
4. Barritt GJ. Receptor-activated Ca2+ inflow in animal cells: a variety of pathways tailored to meet different intracellular Ca2+ signalling requirements. Biochem J 337: 153169, 1999.[CrossRef][ISI][Medline]
5. Berridge MJ. Capacitative calcium entry. Biochem J 312: 111, 1995.[ISI][Medline]
6. Clapham DE. Intracellular calcium: replenishing the stores. Nature 375: 634635, 1995.[CrossRef][ISI][Medline]
7. Communi D, Dewaste V, and Erneux C. Calcium-calmodulin-dependent protein kinase II and protein kinase C-mediated phosphorylation and activation of D-myo-inositol 1,4,5-trisphosphate 3-kinase B in astrocytes. J Biol Chem 274: 1473414742, 1999.
8. Communi D, Gevaert K, Demol H, Vandekerckhove J, and Erneux C. A novel receptor-mediated regulation mechanism of type I inositol polyphosphate 5-phosphatase by calcium/calmodulin-dependent protein kinase II phosphorylation. J Biol Chem 276: 3873838747, 2001.
9. Cui J, Matkovich SJ, deSouza N, Li S, Rosemblit N, and Marks AR. Regulation of the type 1 inositol 1,4,5-trisphosphate receptor by phosphorylation at tyrosine 353. J Biol Chem 279: 1631116316, 2004.
10. Dedkova EN and Blatter LA. Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum Ca2+ uptake in bovine vascular endothelial cells. J Physiol 539: 7791, 2002.
11. DeSouza N, Reiken S, Ondrias K, Yang YM, Matkovich S, and Marks AR. Protein kinase A and two phosphatases are components of the inositol 1,4,5-trisphosphate receptor macromolecular signaling complex. J Biol Chem 277: 3939739400, 2002.
12. Ferris CD, Huganir RL, Bredt DS, Cameron AM, and Snyder SH. Inositol trisphosphate receptor: phosphorylation by protein kinase C and calcium calmodulin-dependent protein kinases in reconstituted lipid vesicles. Proc Natl Acad Sci USA 88: 22322235, 1991.
13. Fleming I, Fisslthaler B, and Busse R. Calcium signaling in endothelial cells involves activation of tyrosine kinases and leads to activation of mitogen-activated protein kinases. Circ Res 76: 522529, 1995.
14. Gailly P. Ca2+ entry in CHO cells, after Ca2+ stores depletion, is mediated by arachidonic acid. Cell Calcium 24: 293304, 1998.[CrossRef][ISI][Medline]
15. Gailly P, Hermans E, and Gillis JM. Role of [Ca2+]i in "Ca2+ stores depletion-Ca2+ entry coupling' in fibroblasts expressing the rat neurotensin receptor. J Physiol 491: 635646, 1996.[Abstract]
16. Hermosura MC, Takeuchi H, Fleig A, Riley AM, Potter BV, Hirata M, and Penner R. InsP4 facilitates store-operated calcium influx by inhibition of InsP3 5-phosphatase. Nature 408: 735740, 2000.[CrossRef][ISI][Medline]
17. Hidaka H and Ishikawa T. Molecular pharmacology of calmodulin pathways in the cell functions. Cell Calcium 13: 465472, 1992.[CrossRef][ISI][Medline]
18. Holda JR and Blatter LA. Capacitative calcium entry is inhibited in vascular endothelial cells by disruption of cytoskeletal microfilaments. FEBS Lett 403: 191196, 1997.[CrossRef][ISI][Medline]
19. Holda JR, Klishin A, Sedova M, Huser J, and Blatter LA. Capacitative Calcium Entry. News Physiol Sci 13: 157163, 1998.[ISI][Medline]
20. Huser J, Holda JR, Kockskamper J, and Blatter LA. Focal agonist stimulation results in spatially restricted Ca2+ release and capacitative Ca2+ entry in bovine vascular endothelial cells. J Physiol 514: 101109, 1999.
21. Irvine RF and Schell MJ. Back in the water: the return of the inositol phosphates. Nat Rev Mol Cell Biol 2: 327338, 2001.[CrossRef][ISI][Medline]
22. Ishida A, Kameshita I, Okuno S, Kitani T, and Fujisawa H. A novel highly specific and potent inhibitor of calmodulin-dependent protein kinase II. Biochem Biophys Res Commun 212: 806812, 1995.[CrossRef][ISI][Medline]
23. Jenner S, Farndale RW, and Sage SO. The effect of calcium-store depletion and refilling with various bivalent cations on tyrosine phosphorylation and Mn2+ entry in fura-2-loaded human platelets. Biochem J 303: 337339, 1994.[ISI][Medline]
24. Kirischuk S, Scherer J, Kettenmann H, and Verkhratsky A. Activation of P2-purinoreceptors triggered Ca2+ release from InsP3-sensitive internal stores in mammalian oligodendrocytes. J Physiol 483: 4157, 1995.[Abstract]
25. Klishin A, Sedova M, and Blatter LA. Time-dependent modulation of capacitative Ca2+ entry signals by plasma membrane Ca2+ pump in endothelium. Am J Physiol Cell Physiol 274: C1117C1128, 1998.
26. Machaca K. Ca2+-calmodulin-dependent protein kinase II potentiates store-operated Ca2+ current. J Biol Chem 278: 3373033737, 2003.
27. Mackenzie L, Bootman MD, Laine M, Berridge MJ, Thuring J, Holmes A, Li WH, and Lipp P. The role of inositol 1,4,5-trisphosphate receptors in Ca2+ signalling and the generation of arrhythmias in rat atrial myocytes. J Physiol 541: 395409, 2002.
28. Madge L, Marshall IC, and Taylor CW. Delayed autoregulation of the Ca2+ signals resulting from capacitative Ca2+ entry in bovine pulmonary artery endothelial cells. J Physiol 498: 351369, 1997.[Abstract]
29. Maruyama T, Kanaji T, Nakade S, Kanno T, and Mikoshiba K. 2APB, 2-aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J Biochem (Tokyo) 122: 498505, 1997.[Abstract]
30. Matifat F, Hague F, Brule G, and Collin T. Regulation of InsP3-mediated Ca2+ release by CaMKII in Xenopus oocytes. Pflügers Arch 441: 796801, 2001.[CrossRef][ISI][Medline]
31. McCullar JS, Larsen SA, Millimaki RA, and Filtz TM. Calmodulin is a phospholipase C- interacting protein. J Biol Chem 278: 3370833713, 2003.
32. Mori M, Hosomi H, Nishizaki T, Kawahara K, and Okada Y. Calcium release from intracellular stores evoked by extracellular ATP in a Xenopus renal epithelial cell line. J Physiol 502: 365373, 1997.[Abstract]
33. Nadif Kasri N, Bultynck G, Sienaert I, Callewaert G, Erneux C, Missiaen L, Parys JB, and De Smedt H. The role of calmodulin for inositol 1,4,5-trisphosphate receptor function. Biochim Biophys Acta 1600: 1931, 2002.[ISI][Medline]
34. Norwood N, Moore TM, Dean DA, Bhattacharjee R, Li M, and Stevens T. Store-operated calcium entry and increased endothelial cell permeability. Am J Physiol Lung Cell Mol Physiol 279: L815L824, 2000.
35. O'Neill AF, Hagar RE, Zipfel WR, Nathanson MH, and Ehrlich BE. Regulation of the type III InsP3 receptor by InsP3 and calcium. Biochem Biophys Res Commun 294: 719725, 2002.[CrossRef][ISI][Medline]
36. Pacaud P, Gregoire G, and Loirand G. Release of Ca2+ from intracellular store in smooth muscle cells of rat portal vein by ATP-induced Ca2+ entry. Br J Pharmacol 113: 457462, 1994.[ISI][Medline]
37. Parekh AB, Terlau H, and Stuhmer W. Depletion of InsP3 stores activates a Ca2+ and K+ current by means of a phosphatase and a diffusible messenger. Nature 364: 814818, 1993.[CrossRef][ISI][Medline]
38. Patel RJ, Prajapati KD, Arun KHS, and Thyagarajan B. Ca2+ trapped in smooth muscle cell signaling web. CRIPS Curr Res Inf Pharm Sci 4: 27, 2003.
39. Peppiatt CM, Collins TJ, Mackenzie L, Conway SJ, Holmes AB, Bootman MD, Berridge MJ, Seo JT, and Roderick HL. 2-Aminoethoxydiphenyl borate (2-APB) antagonises inositol 1,4,5-trisphosphate-induced calcium release, inhibits calcium pumps and has a use-dependent and slowly reversible action on store-operated calcium entry channels. Cell Calcium 34: 97108, 2003.[ISI][Medline]
40. Putney JW Jr and McKay RR. Capacitative calcium entry channels. Bioessays 21: 3846, 1999.[CrossRef][ISI][Medline]
41. Richard EA, Ghosh S, Lowenstein JM, and Lisman JE. Ca2+/calmodulin-binding peptides block phototransduction in Limulus ventral photoreceptors: evidence for direct inhibition of phospholipase C. Proc Natl Acad Sci USA 94: 1409514099, 1997.
42. Sedova M and Blatter LA. Dynamic regulation of [Ca2+]i by plasma membrane Ca2+-ATPase and Na+/Ca2+ exchange during capacitative Ca2+ entry in bovine vascular endothelial cells. Cell Calcium 25: 333343, 1999.[CrossRef][ISI][Medline]
43. Sedova M, Klishin A, Huser J, and Blatter LA. Capacitative Ca2+ entry is graded with degree of intracellular Ca2+ store depletion in bovine vascular endothelial cells. J Physiol 523: 549559, 2000.
44. Sharma NR and Davis MJ. Calcium entry activated by store depletion in coronary endothelium is promoted by tyrosine phosphorylation. Am J Physiol Heart Circ Physiol 270: H267H274, 1996.
45. Supattapone S, Danoff SK, Theibert A, Joseph SK, Steiner J, and Snyder SH. Cyclic AMP-dependent phosphorylation of a brain inositol trisphosphate receptor decreases its release of calcium. Proc Natl Acad Sci USA 85: 87478750, 1988.
46. Svichar N, Shmigol A, Verkhratsky A, and Kostyuk P. InsP3-induced Ca2+ release in dorsal root ganglion neurones. Neurosci Lett 227: 107110, 1997.[CrossRef][ISI][Medline]
47. Takahashi R, Watanabe H, Zhang XX, Kakizawa H, Hayashi H, and Ohno R. Roles of inhibitors of myosin light chain kinase and tyrosine kinase on cation influx in agonist-stimulated endothelial cells. Biochem Biophys Res Commun 235: 657662, 1997.[CrossRef][ISI][Medline]
48. Tang TS, Tu H, Wang Z, and Bezprozvanny I. Modulation of type 1 inositol (1,4,5)-trisphosphate receptor function by protein kinase A and protein phosphatase 1. J Neurosci 23: 403415, 2003.
49. Taylor CW and Laude AJ. IP3 receptors and their regulation by calmodulin and cytosolic Ca2+. Cell Calcium 32: 321334, 2002.[CrossRef][ISI][Medline]
50. Tornquist K and Ekokoski E. Inhibition of agonist-mediated calcium entry by calmodulin antagonists and by the Ca2+/calmodulin kinase II inhibitor KN-62: studies with thyroid FRTL-5 cells. J Endocrinol 148: 131138, 1996.[Abstract]
51. Tran QK, Watanabe H, Le HY, Pan L, Seto M, Takeuchi K, and Ohashi K. Myosin light chain kinase regulates capacitative Ca2+ entry in human monocytes/macrophages. Arterioscler Thromb Vasc Biol 21: 509515, 2001.
52. Vazquez G, de Boland AR, and Boland RL. Involvement of calmodulin in 1,25-dihydroxyvitamin D3 stimulation of store-operated Ca2+ influx in skeletal muscle cells. J Biol Chem 275: 1613416138, 2000.
53. Volpe P and Alderson-Lang BH. Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release II Effect of cAMP-dependent protein kinase. Am J Physiol Cell Physiol 258: C1086C1091, 1990.
54. Vostal JG, Jackson WL, and Shulman NR. Cytosolic and stored calcium antagonistically control tyrosine phosphorylation of specific platelet proteins. J Biol Chem 266: 1691116916, 1991.
55. Wang KK, Du YS, Diglio C, Tsang W, and Kuo TH. Hormone-induced phosphorylation of the plasma membrane calcium pump in cultured aortic endothelial cells. Arch Biochem Biophys 289: 103108, 1991.[CrossRef][ISI][Medline]
56. Watanabe H, Takahashi R, Zhang XX, Goto Y, Hayashi H, Ando J, Isshiki M, Seto M, Hidaka H, Niki I, and Ohno R. An essential role of myosin light-chain kinase in the regulation of agonist- and fluid flow-stimulated Ca2+ influx in endothelial cells. FASEB J 12: 341348, 1998.
57. Watanabe H, Takahashi R, Zhang XX, Kakizawa H, Hayashi H, and Ohno R. Inhibition of agonist-induced Ca2+ entry in endothelial cells by myosin light-chain kinase inhibitor. Biochem Biophys Res Commun 225: 777784, 1996.[CrossRef][ISI][Medline]
58. Zhu DM, Tekle E, Chock PB, and Huang CY. Reversible phosphorylation as a controlling factor for sustaining calcium oscillations in HeLa cells: Involvement of calmodulin-dependent kinase II and a calyculin A-inhibitable phosphatase. Biochemistry 35: 72147223, 1996.[CrossRef][ISI][Medline]
59. Zima AV and Blatter LA. Inositol-1,4,5-trisphosphate-dependent Ca2+ signalling in cat atrial excitation-contraction coupling and arrhythmias. J Physiol 555: 607615, 2004.
|
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Visit Other APS Journals Online |