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1.
The cytoplasmic Ca2+ concentration ([Ca2+]cyt) in resting cells in an equilibrium between several influx and efflux mechanisms. Here we address the question of whether capacitative Ca2+ entry to some extent is active at resting conditions and therefore is part of processes that guarantee a constant [Ca2+]cyt. We measured changes of [Ca2+]cyt in RBL-1 cells with fluorometric techniques. An increase of the extracellular [Ca2+] from 1.3 mM to 5 mM induced an incrase in [Ca2+]cyt from 105±10 nM to 145±8.5 nM. This increase could be inhibited by 10 μM Gd3+, 10 μM La3+ or 50 μM 2-aminoethoxydiphenyl borate, blockers of capacitative Ca2+ entry. Application of those blockers to a resting cell in a standard extracellular solution (1.3 mM Ca2+) resulted in a decrease of [Ca2+]cyt from 105±10 nM to 88.5±10 nM with La3+, from 103±12 to 89±12 nM with Gd3+ and from 102±12 nM to 89.5±5 nM with 2-aminoethoxydiphenyl borate. From these data, we conclude that capacitative Ca2+ entry beside its function in Ca2+ signaling contributes to the regulation of resting [Ca2+]cyt.  相似文献   

2.
Large-conductance Ca2+-dependent K+ (BKCa) channels are activated by intracellular Ca2+ and membrane depolarization in an allosteric manner. We investigated the pharmacological and biophysical characteristics of a BKCa-type K+ channel in androgen-dependent LNCaP (lymph node carcinoma of the prostate) cells with novel functional properties, here termed BKL. K+ selectivity, high conductance, activation by Mg2+ or NS1619, and inhibition by paxilline and penitrem A largely resembled the properties of recombinant BKCa channels. However, unlike conventional BKCa channels, BKL channels activated in the absence of free cytosolic Ca2+ at physiological membrane potentials; the half-maximal activation voltage was shifted by about −100 mV compared with BKCa channels. Half-maximal Ca2+-dependent activation was observed at 0.4 μM for BKL (at −20 mV) and at 4.1 μM for BKCa channels (at +50 mV). Heterologous expression of hSlo1 in LNCaP cells increased the BKL conductance. Expression of hSlo-β1 in LNCaP cells shifted voltage-dependent activation to values between that of BKL and BKCa channels and reduced the slope of the Popen (open probability)-voltage curve. We propose that LNCaP cells harbor a so far unknown type of BKCa subunit, which is responsible for the BKL phenotype in a dominant manner. BKL-like channels are also expressed in the human breast cancer cell line T47D. In addition, functional expression of BKL in LNCaP cells is regulated by serum-derived factors, however not by androgens.  相似文献   

3.
The primary target for cocaine is believed to be monoamine transporters because of cocaine’s high-affinity binding that prevents re-uptake of released neurotransmitter. However, direct interaction with ion channels has been shown to be important for certain pharmacological/toxicological effects of cocaine. Here I show that cocaine selectively blocks a calcium-dependent K+ channel in hippocampal neurons grown in culture (IC50 = ∼30 μM). Single-channel recordings show that in the presence of cocaine, the channel openings are interrupted with brief closures (flicker block). As the concentration of cocaine is increased the open-time is reduced, whereas the duration of brief closures is independent of concentration. The association and dissociation rate constants of cocaine for the neuronal Ca2+-activated K+ channels are 261 ± 37 μM−1s−1 and 11451 ± 1467 s−1. The equilibrium dissociation constant (KB) for cocaine, determined from single-channel parameters, is 43 μM. The lack of voltage dependence of block suggests that cocaine probably binds to a site at the mouth of the pore. Block of Ca2+-dependent K+ channels by cocaine may be involved in functions that include broadening of the action potential, which would facilitate transmitter release, enhancement of smooth muscle contraction particularly in blood vessels, and modulation of repetitive neuronal firing by altering the repolarization and afterhyperpolarization phases of the action potential.  相似文献   

4.
ATP-dependent Sr2+ transport was examined in vitro using basolateral membrane (BLM) vesicles isolated from rat renal cortex to clarify the discrimination mechanisms between strontium (Sr) and calcium (Ca) in renal tubules during reabsorption. ATP-dependent Sr2+ uptake and Ca2+ uptake were observed in renal BLM vesicles and were inhibited by vanadate. Hill plots indicate similar kinetic behavior for Ca2+ and Sr2+ uptake. The apparentK m andV max of ATP-dependent Sr2+ uptake were both higher than those for Ca2+ uptake. ATP-dependent Sr2+ uptake by BLM vesicles diminished in the presence of 0.1 μM Ca2+ and was more markedly inhibited by 1 μM Ca2+. Hill plots of Sr2+ uptake data with and without 0.1 μM Ca2+ showed that the cooperative behavior of Sr2+ uptake was not changed by Ca2+. In the presence of 0.1 μM Ca2+, the affinity of the transport system for Sr2+ and the velocity of Sr2+ uptake in the BLM were both decreased. However, the rate of Ca2+ uptake was not diminished by Sr2+ concentrations of <1.6 μM. These results suggest that Ca2+ is preferentially transported in the renal cortex BLM when Ca2+ and Sr2+ are present at the same time.  相似文献   

5.
K+-conductive pathways were evaluated in isolated surface and crypt colonic cells, by measuring 86Rb efflux. In crypt cells, basal K+ efflux (rate constant: 0.24 ± 0.044 min−1, span: 24 ± 1.3%) was inhibited by 30 mM TEA and 5 mM Ba2+ in an additive way, suggesting the existence of two different conductive pathways. Basal efflux was insensitive to apamin, iberiotoxin, charybdotoxin and clotrimazole. Ionomycin (5 μM) stimulated K+ efflux, increasing the rate constant to 0.65 ± 0.007 min−1 and the span to 83 ± 3.2%. Ionomycin-induced K+ efflux was inhibited by clotrimazole (IC50 of 25 ± 0.4 μM) and charybdotoxin (IC50 of 65 ± 5.0 nM) and was insensitive to TEA, Ba2+, apamin and iberiotoxin, suggesting that this conductive pathway is related to the Ca2+-activated intermediate-conductance K+ channels (IKca). Absence of extracellular Ca2+ did neither affect basal nor ionomycin-induced K+ efflux. However, intracellular Ca2+ depletion totally inhibited the ionomycin-induced K+ efflux, indicating that the activation of these K+ channels mainly depends on intracellular calcium liberation. K+ efflux was stimulated by intracellular Ca2+ with an EC50 of 1.1 ± 0.04 μM. In surface cells, K+ efflux (rate constant: 0.17 ± 0.027 min−1; span: 25 ± 3.4%) was insensitive to TEA and Ba2+. However, ionomycin induced K+ efflux with characteristics identical to that observed in crypt cells. In conclusion, both surface and crypt cells present IKCa channels but only crypt cells have TEA- and Ba2+-sensitive conductive pathways, which would determine their participation in colonic K+ secretion.  相似文献   

6.
Calcium signaling by cyclic ADP-ribose and NAADP   总被引:4,自引:0,他引:4  
Ca2+ mobilization as a signaling mechanism has been placed on center stage with the discovery of the first Ca2+ messenger, inositol trisphosphate (IP3). This article focuses on two new Ca2+ release activators, which mobilize internal Ca2+ stores via mechanisms totally independent of IP3. They are cyclic ADP-ribose (cADPR) and nicotinic acid dinucleotide phosphate (NAADP), metabolites derived respectively from NAD and NADP. Major advances in the past decade in the understanding of these two novel signaling mechanisms are chronologically summarized.  相似文献   

7.
The concept advanced by Berridge and colleagues that intracellular Ca2+-stores can be mobilized in an agonist-dependent and messenger (IP3)-mediated manner has put Ca2+-mobilization at the center stage of signal transduction mechanisms. During the late 1980s, we showed that Ca2+-stores can be mobilized by two other messengers unrelated to inositol trisphosphate (IP3) and identified them as cyclic ADP-ribose (cADPR), a novel cyclic nucleotide from NAD, and nicotinic acid adenine dinucleotide phosphate (NAADP), a linear metabolite of NADP. Their messenger functions have now been documented in a wide range of systems spanning three biological kingdoms. Accumulated evidence indicates that the target of cADPR is the ryanodine receptor in the sarco/endoplasmic reticulum, while that of NAADP is the two pore channel in endolysosomes.  相似文献   

8.
Nicotinic acid adenine dinucleotide phosphate is an evolutionarily conserved second messenger, which mobilizes Ca2+ from acidic stores. The molecular identity of the NAADP receptor has yet to be defined. In pursuit of isolating and identifying NAADP-binding proteins, we synthesized and characterized a bifunctional probe that incorporates both a photoactivatable crosslinking azido moiety at the 5-position of the nicotinic ring and a ‘clickable’ ethynyl moiety to the 8-adenosyl position in NAADP. Microinjection of this 5N3-8-ethynyl-NAADP into cultured U2OS cells induced robust Ca2+ responses. Higher concentrations of 5N3-8-ethynyl were required to elicit Ca2+ release or displace 32P-NAADP in radioligand binding experiments in sea urchin egg homogenates. In human cell extracts, incubation of 32P-5N3-8-ethynyl-NAADP followed by UV irradiation resulted in selective labeling of 23 kDa and 35 kDa proteins and photolabeling of these proteins was prevented when incubated in the presence of unlabeled NAADP. Compared to the monofunctional 32P-5N3-NAADP, the clickable 32P-5N3-8-ethynyl-NAADP demonstrated less labeling of the 23 kDa and 35 kDa proteins (~3-fold) but provided an opportunity for further enrichment through the ‘clickable’ ethynyl moiety. No proteins were specifically labeled by 32P-5N3-8-ethynyl-NAADP in sea urchin egg homogenate. These experiments demonstrate that 5N3-8-ethynyl-NAADP is biologically active and selectively labels putative NAADP-binding proteins in mammalian systems, evidencing a ‘bifunctional’ probe with utility for isolating NAADP-binding proteins.  相似文献   

9.
The second messenger NAADP triggers Ca2+ release from endo-lysosomes. Although two-pore channels (TPCs) have been proposed to be regulated by NAADP, recent studies have challenged this. By generating the first mouse line with demonstrable absence of both Tpcn1 and Tpcn2 expression (Tpcn1/2−/−), we show that the loss of endogenous TPCs abolished NAADP-dependent Ca2+ responses as assessed by single-cell Ca2+ imaging or patch-clamp of single endo-lysosomes. In contrast, currents stimulated by PI(3,5)P2 were only partially dependent on TPCs. In Tpcn1/2−/− cells, NAADP sensitivity was restored by re-expressing wild-type TPCs, but not by mutant versions with impaired Ca2+-permeability, nor by TRPML1. Another mouse line formerly reported as TPC-null likely expresses truncated TPCs, but we now show that these truncated proteins still support NAADP-induced Ca2+ release. High-affinity [32P]NAADP binding still occurs in Tpcn1/2−/− tissue, suggesting that NAADP regulation is conferred by an accessory protein. Altogether, our data establish TPCs as Ca2+-permeable channels indispensable for NAADP signalling.  相似文献   

10.
Cell calcium is accumulated in intracellular stores by sarco-endoplasmic reticulum Ca2+ ATPases functionally interacting with the membrane lipid environment. Cold adaptations of membrane lipids in Antarctic Sea organisms suggest possible adaptive effects also on sarco-endoplasmic reticulum Ca2+ ATPases. We investigated the SR Ca2+ ATPase of an Antarctic scallop, Adamussium colbecki, by characterising the enzyme activity and studying temperature effects. Ca2+ ATPase, assayed by following ATP hydrolysis, was thapsigargin- and vanadate-sensitive, showed maximum activity under 2 μM Ca2+, 200 mM KCl and pH 7.2, and had a K M for ATP of 22 ± 7 μM. Temperature effects showed an Arrhenius inversion between −1.8 and 0°C, indicating cold adaptation, an Arrhenius break at 10°C, and a collapse above 20°C. A. colbecki accumulates high amounts of cadmium in the digestive gland; heavy metal effects on sarco-endoplasmic reticulum Ca2+ ATPases were therefore tested, finding an IC50 = 0.9 μM for Hg2+ and 3 μM for Cd2+. Finally, SDS-PAGE analysis showed a main band at about 100 kDa, which was identified as sarco-endoplasmic reticulum Ca2+ ATPase after trypsin digestion, and accounted for 60% total protein. Accepted: 10 December 1998  相似文献   

11.
The roles of Ca2+ mobilization in development of tension induced by acetylcholine (ACh, 0.1–100 µM) in swine tracheal smooth muscle strips were studied. Under control conditions, ACh induced a transient increase in free cytosolic calcium concentration ([Ca2+]i) that declined to a steady-state level. The peak increase in [Ca2+]i correlated with the magnitude of tension at each [ACh] after a single exposure to ACh, while the steady-state [Ca2+]i did not. Removal of extracellular Ca2+ had little effect on peak [Ca2+]i but greatly reduced steady-state increases in [Ca2+]i and tension. Verapamil inhibited steady-state [Ca2+]i only at [ACh]<1 µM. After depletion of internal Ca2+ stores by 10 min exposure to ACh in Ca2+-free solution and then washout of ACh for 5 min in Ca2+-free solution, simultaneous re-exposure to ACh in the presence of 2.5 mM Ca2+ increased [Ca2+]i to the control steady-state level without overshoot. The tension attained was the same as control for each [ACh] used. Continuous exposure to successively increasing [ACh] (0.1–100 µM) also reduced the overshoot of [Ca2+]i at 10 and 100 µM ACh, yet tension reached control levels at each [ACh] used. We conclude that the steady-state increase in [Ca2+]i is necessary for tension maintenance and is dependent on Ca2+ influx through voltage-gated calcium channels at 0.1 µM ACh and through a verapamil-insensitive pathway at 10 and 100 µM. The initial transient increase in calcium arises from intracellular stores and is correlated with the magnitude of tension only in muscles that have completely recovered from previous exposure to agonists.  相似文献   

12.
Effects of intracellular Mg2+ on a native Ca2+-and voltage-sensitive large-conductance K+ channel in cultured human renal proximal tubule cells were examined with the patch-clamp technique in the inside-out mode. At an intracellular concentration of Ca2+ ([Ca2+]i) of 10−5–10−4 M, addition of 1–10 mM Mg2+ increased the open probability (Po) of the channel, which shifted the Po –membrane potential (Vm) relationship to the negative voltage direction without causing an appreciable change in the gating charge (Boltzmann constant). However, the Mg2+-induced increase in Po was suppressed at a relatively low [Ca2+]i (10−5.5–10−6 M). Dwell-time histograms have revealed that addition of Mg2+ mainly increased Po by extending open times at 10−5 M Ca2+ and extending both open and closed times simultaneously at 10−5.5 M Ca2+. Since our data showed that raising the [Ca2+]i from 10−5 to 10−4 M increased Po mainly by shortening the closed time, extension of the closed time at 10−5.5 M Ca2+ would result from the Mg2+-inhibited Ca2+-dependent activation. At a constant Vm, adding Mg2+ enhanced the sigmoidicity of the Po–[Ca2+]i relationship with an increase in the Hill coefficient. These results suggest that the major action of Mg2+ on this channel is to elevate Po by lengthening the open time, while extension of the closed time at a relatively low [Ca2+]i results from a lowering of the sensitivity to Ca2+ of the channel by Mg2+, which causes the increase in the Hill coefficient. M. Kubokawa and Y. Sohma contributed equally to this work.  相似文献   

13.
This combined study of patch-clamp and intracellular Ca2+ ([Ca2+] i ) measurement was undertaken in order to identify signaling pathways that lead to activation of Ca2+-dependent Cl channels in cultured rat retinal pigment epithelial (RPE) cells. Intracellular application of InsP3 (10 μm) led to an increase in [Ca2+] i and activation of Cl currents. In contrast, intracellular application of Ca2+ (10 μm) only induced transient activation of Cl currents. After full activation by InsP3, currents were insensitive to removal of extracellular Ca2+ and to the blocker of I CRAC, La3+ (10 μm), despite the fact that both maneuvers led to a decline in [Ca2+] i . The InsP3-induced rise in Cl conductance could be prevented either by thapsigargin-induced (1 μm) depletion of intracellular Ca2+ stores or by removal of Ca2+ prior to the experiment. The effect of InsP3 could be mimicked by intracellular application of the Ca2+-chelator BAPTA (10 mm). Block of PKC (chelerythrine, 1 μm) had no effect. Inhibition of Ca2+/calmodulin kinase (KN-63, KN-92; 5 μm) reduced Cl-conductance in 50% of the cells investigated without affecting [Ca2+] i . Inhibition of protein tyrosine kinase (50 μm tyrphostin 51, 5 μm genistein, 5 μm lavendustin) reduced an increase in [Ca2+] i and Cl conductance. In summary, elevation of [Ca] i by InsP3 leads to activation of Cl channels involving cytosolic Ca2+ stores and Ca2+ influx from extracellular space. Tyrosine kinases are essential for the Ca2+-independent maintenance of this conductance. Received: 15 October 1998/Revised: 3 March 1999  相似文献   

14.
The effect of ANG II on pHi, [Ca2+]i and cell volume was investigated in T84 cells, a cell line originated from colon epithelium, using the probes BCECF-AM, Fluo 4-AM and acridine orange, respectively. The recovery rate of pHi via the Na+/H+ exchanger was examined in the first 2 min following the acidification of pHi with a NH4Cl pulse. In the control situation, the pHi recovery rate was 0.118 ± 0.001 (n = 52) pH units/min and ANG II (10−12 M or 10−9 M) increased this value (by 106% or 32%, respectively) but ANG II (10−7 M) decreased it to 47%. The control [Ca2+]i was 99 ± 4 (n = 45) nM and ANG II increased this value in a dose-dependent manner. The ANG II effects on cell volume were minor and late and should not interfere in the measurements of pHi recovery and [Ca2+]i. To document the signaling pathways in the hormonal effects we used: Staurosporine (a PKC inhibitor), W13 (a calcium-dependent calmodulin antagonist), H89 (a PKA inhibitor) or Econazole (an inhibitor of cytochrome P450 epoxygenase). Our results indicate that the biphasic effect of ANG II on Na+/H+ exchanger is a cAMP-independent mechanism and is the result of: 1) stimulation of the exchanger by PKC signaling pathway activation (at 10−12 – 10−7 M ANG II) and by increases of [Ca2+]i in the lower range (at 10−12 M ANG II) and 2) inhibition of the exchanger at high [Ca2+]i levels (at 10−9 – 10−7 M ANG II) through cytochrome P450 epoxygenase-dependent metabolites of the arachidonic acid signaling pathway.  相似文献   

15.
UV irradiation has multiple effects on mammalian cells, including modification of ion channel function. The present study was undertaken to investigate the response of membrane currents in guinea-pig ventricular myocytes to the type A (355, 380 nm) irradiation commonly used in Ca2+ imaging studies. Myocytes configured for whole-cell voltage clamp were generally held at −80 mV, dialyzed with K+-, Na+-free pipette solution, and bathed with K+-free Tyrode’s solution at 22°C. During experiments that lasted for ≈ 35 min, UVA irradiation caused a progressive increase in slowly-inactivating inward current elicited by 200-ms depolarizations from −80 to −40 mV, but had little effect on background current or on L-type Ca2+ current. Trials with depolarized holding potential, Ca2+ channel blockers, and tetrodotoxin (TTX) established that the current induced by irradiation was late (slowly-inactivating) Na+ current (INa). The amplitude of the late inward current sensitive to 100 μM TTX was increased by 3.5-fold after 20–30 min of irradiation. UVA modulation of late INa may (i) interfere with imaging studies, and (ii) provide a paradigm for investigation of intracellular factors likely to influence slow inactivation of cardiac INa.  相似文献   

16.
The aim of this study was to quantify the glucose modulation of the plasma membrane calcium pump (PMCA) function in rat pancreatic islets. Ca2+-ATPase activity and levels of phosphorylated PMCA intermediates both transiently declined to a minimum in response to stimulation by glucose. Strictly dependent on Ca2+ concentration, this inhibitory effect was fully expressed at physiological concentrations of the cation (less than 0.5 μM), then progressively diminished at higher concentrations. These results, together with those previously reported on the effects of insulin secretagogues and blockers on the activity, expression and cellular distribution of the PMCA, support the concept that the PMCA plays a key role in the regulation of Ca2+ signaling and insulin secretion in pancreatic islets.  相似文献   

17.
1. Cultured dorsal root ganglion neurons of rat pups were depolarized by exposure to 50 mM K+ and the rise of [Ca2+]i was measured using fura-2 as an indicator.2. Lead in the extracellular solution reduced the rise of [Ca2+]i in a concentration-dependent manner, with a threshold concentration of 0.25 M. More than 80% of the calcium entry was prevented by 5 M lead. The IC50 and the Hill coefficient were 1.3 M and 1, respectively.3. This effect was considered to be due to a reduction of VACCCs, since applications of NMDA did not result in any rise of [Ca2+]i.4. Since Pb2+ itself changes the fura-2 signal in a typical and characteristic manner, fura-2 is also an indicator for Pb2+. No changes in fura-2 signals were detected when lead (5 M) was applied for several minutes in the absence of calcium, indicating that Pb2+ did not enter the cells.5. Thus it is concluded that lead prevents calcium entry by reducing VACCCs but does not cross the cell membrane itself.  相似文献   

18.
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+ mobilizing second messenger which triggers Ca2+ release in both sea urchin egg homogenates and in mammalian cells. The NAADP binding protein has not been identified and the regulation of NAADP mediated Ca2+ release remains controversial. To address this issue, we have synthesized an NAADP analog in which 3-azido-5-azidomethylbenzoic acid is attached to the amino group of 5-(3-aminopropyl)-NAADP to produce an NAADP analog which is both a photoaffinity label and clickable. This ‘all-in-one-clickable’ NAADP (AIOC-NAADP) elicited Ca2+ release when microinjected into cultured human SKBR3 cells at low concentrations. In contrast, it displayed little activity in sea urchin egg homogenates where very high concentrations were required to elicit Ca2+ release. In mammalian cell homogenates, incubation with low concentrations of [32P]AIOC-NAADP followed by irradiation with UV light resulted in labeling 23 kDa protein(s). Competition between [32P]AIOC-NAADP and increasing concentrations of NAADP demonstrated that the labeling was selective. We show that this label recognizes and selectively photodervatizes the 23 kDa NAADP binding protein(s) in cultured human cells identified in previous studies using [32P]5-N3-NAADP.  相似文献   

19.
Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable cation channel involved in physiological and pathophysiological processes linked to oxidative stress. TRPM2 channels are co-activated by intracellular Ca2+ and ADP-ribose (ADPR) but also modulated in intact cells by several additional factors. Superfusion of TRPM2-expressing cells with H2O2 or intracellular dialysis of cyclic ADPR (cADPR) or nicotinic acid adenine dinucleotide phosphate (NAADP) activates, whereas dialysis of AMP inhibits, TRPM2 whole-cell currents. Additionally, H2O2, cADPR, and NAADP enhance ADPR sensitivity of TRPM2 currents in intact cells. Because in whole-cell recordings the entire cellular machinery for nucleotide and Ca2+ homeostasis is intact, modulators might affect TRPM2 activity either directly, by binding to TRPM2, or indirectly, by altering the local concentrations of the primary ligands ADPR and Ca2+. To identify direct modulators of TRPM2, we have studied the effects of H2O2, AMP, cADPR, NAADP, and nicotinic acid adenine dinucleotide in inside-out patches from Xenopus oocytes expressing human TRPM2, by directly exposing the cytosolic faces of the patches to these compounds. H2O2 (1 mm) and enzymatically purified cADPR (10 μm) failed to activate, whereas AMP (200 μm) failed to inhibit TRPM2 currents. NAADP was a partial agonist (maximal efficacy, ∼50%), and nicotinic acid adenine dinucleotide was a full agonist, but both had very low affinities (K0.5 = 104 and 35 μm). H2O2, cADPR, and NAADP did not enhance activation by ADPR. Considering intracellular concentrations of these compounds, none of them are likely to directly affect the TRPM2 channel protein in a physiological context.  相似文献   

20.
Many physiological processes are controlled by a great diversity of Ca2 + signals that depend on Ca2 + entry into the cell and/or Ca2 + release from internal Ca2 + stores. Ca2 + mobilization from intracellular stores is gated by a family of messengers including inositol-1,4,5-trisphosphate (InsP3), cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP). There is increasing evidence for a novel intracellular Ca2 + release channel that may be targeted by NAADP and that displays properties distinctly different from the well-characterized InsP3 and ryanodine receptors. These channels appear to localize on a wider range of intracellular organelles, including the acidic Ca2 + stores. Activation of the NAADP-sensitive Ca2 + channels evokes complex changes in cytoplasmic Ca2 + levels by means of channel chatter with other intracellular Ca2 + channels. The recent demonstration of changes in intracellular NAADP levels in response to physiologically relevant extracellular stimuli highlights the significance of NAADP as an important regulator of intracellular Ca2 + signaling.  相似文献   

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