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1.
Sergio de la Fuente 《BBA》2010,1797(10):1727-1735
We have investigated the kinetics of mitochondrial Ca2+ influx and efflux and their dependence on cytosolic [Ca2+] and [Na+] using low-Ca2+-affinity aequorin. The rate of Ca2+ release from mitochondria increased linearly with mitochondrial [Ca2+] ([Ca2+]M). Na+-dependent Ca2+ release was predominant al low [Ca2+]M but saturated at [Ca2+]M around 400 μM, while Na+-independent Ca2+ release was very slow at [Ca2+]M below 200 μM, and then increased at higher [Ca2+]M, perhaps through the opening of a new pathway. Half-maximal activation of Na+-dependent Ca2+ release occurred at 5-10 mM [Na+], within the physiological range of cytosolic [Na+]. Ca2+ entry rates were comparable in size to Ca2+ exit rates at cytosolic [Ca2+] ([Ca2+]c) below 7 μM, but the rate of uptake was dramatically accelerated at higher [Ca2+]c. As a consequence, the presence of [Na+] considerably reduced the rate of [Ca2+]M increase at [Ca2+]c below 7 μM, but its effect was hardly appreciable at 10 μM [Ca2+]c. Exit rates were more dependent on the temperature than uptake rates, thus making the [Ca2+]M transients to be much more prolonged at lower temperature. Our kinetic data suggest that mitochondria have little high affinity Ca2+ buffering, and comparison of our results with data on total mitochondrial Ca2+ fluxes indicate that the mitochondrial Ca2+ bound/Ca2+ free ratio is around 10- to 100-fold for most of the observed [Ca2+]M range and suggest that massive phosphate precipitation can only occur when [Ca2+]M reaches the millimolar range. 相似文献
2.
Sergey M. Korotkov 《Journal of bioenergetics and biomembranes》2009,41(3):277-287
It is known that permeability of the inner mitochondrial membrane is low to most univalent cations (K+, Na+, H+) but high to Tl+. Swelling, state 4, state 3, and 2,4-dinitrophenol (DNP)-stimulated respiration as well as the membrane potential (ΔΨmito) of rat liver mitochondria were studied in media containing 0–75 mM TlNO3 either with 250 mM sucrose or with 125 mM nitrate salts of other monovalent cations (KNO3, or NaNO3, or NH4NO3). Tl+ increased permeability of the inner mitochondrial membrane to K+, Na+, and H+, that was manifested as stimulation of the swelling of nonenergized and energized mitochondria as well as via an increase
of state 4 and dissipation of ΔΨmito. These effects of Tl+ increased in the order of sucrose <K+ <Na+ ≤ NH4+. They were stimulated by inorganic phosphate and decreased by ADP, Mg2+, and cyclosporine A. Contraction of energized mitochondria, swollen in the nitrate media, was markedly inhibited by quinine.
It suggests participation of the mitochondrial K+/H+ exchanger in extruding of Tl+-induced excess of univalent cations from the mitochondrial matrix. It is discussed that Tl+ (like Cd2+ and other heavy metals) increases the ion permeability of the inner membrane of mitochondria regardless of their energization
and stimulates the mitochondrial permeability transition pore in low conductance state. The observed decrease of state 3 and
DNP-stimulated respiration in the nitrate media resulted from the mitochondrial swelling rather than from an inhibition of
respiratory enzymes as is the case with the bivalent heavy metals. 相似文献
3.
Mitochondria in Ca2+ Signaling and Apoptosis 总被引:8,自引:0,他引:8
Soraya S. Smaili Yi-Te Hsu Richard J. Youle James T. Russell 《Journal of bioenergetics and biomembranes》2000,32(1):35-46
Cellular Ca2+ signals are crucial in the control of most physiological processes, cell injuryand programmed cell death; mitochondria play a pivotal role in the regulation of such cytosolicCa2+ ([Ca2+]c) signals. Mitochondria are endowed with multiple Ca2+ transport mechanismsby which they take up and release Ca2+ across their inner membrane. These transport processesfunction to regulate local and global [Ca2+]c, thereby regulating a number of Ca2+-sensitivecellular mechanisms. The permeability transition pore (PTP) forms the major Ca2+ effluxpathway from mitochondria. In addition, Ca2+ efflux from the mitochondrial matrix occursby the reversal of the uniporter and through the inner membrane Na+/Ca2+ exchanger. Duringcellular Ca2+ overload, mitochondria take up [Ca2+]c, which, in turn, induces opening of PTP,disruption of mitochondrial membrane potential (m) and cell death. In apoptosis signaling,collapse of ;m and cytochrome c release from mitochondria occur followed by activationof caspases, DNA fragmentation, and cell death. Translocation of Bax, an apoptotic signalingprotein from the cytosol to the mitochondrial membrane, is another step during thisapoptosis-signaling pathway. The role of permeability transition in the context of cell death in relationto Bcl-2 family of proteins is discussed. 相似文献
4.
Vladimir Parpura Vladimir Grubiši?Alexei Verkhratsky 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(5):984-991
Astrocytes can exocytotically release the gliotransmitter glutamate from vesicular compartments. Increased cytosolic Ca2+ concentration is necessary and sufficient for this process. The predominant source of Ca2+ for exocytosis in astrocytes resides within the endoplasmic reticulum (ER). Inositol 1,4,5-trisphosphate and ryanodine receptors of the ER provide a conduit for the release of Ca2+ to the cytosol. The ER store is (re)filled by the store-specific Ca2+-ATPase. Ultimately, the depleted ER is replenished by Ca2+ which enters from the extracellular space to the cytosol via store-operated Ca2+ entry; the TRPC1 protein has been implicated in this part of the astrocytic exocytotic process. Voltage-gated Ca2+ channels and plasma membrane Na+/Ca2+ exchangers are additional means for cytosolic Ca2+ entry. Cytosolic Ca2+ levels can be modulated by mitochondria, which can take up cytosolic Ca2+ via the Ca2+ uniporter and release Ca2+ into cytosol via the mitochondrial Na+/Ca2+ exchanger, as well as by the formation of the mitochondrial permeability transition pore. The interplay between various Ca2+ sources generates cytosolic Ca2+ dynamics that can drive Ca2+-dependent exocytotic release of glutamate from astrocytes. An understanding of this process in vivo will reveal some of the astrocytic functions in health and disease of the brain. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. 相似文献
5.
Sirvent P Mercier J Vassort G Lacampagne A 《Biochemical and biophysical research communications》2005,329(3):1067-1075
Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Besides tremendous beneficial effects of statins, various forms of muscular toxicity (myalgia, cramp, exercise intolerance, and fatigability) occur frequently. We hypothesized that the iatrogenic effects of statins could result from alterations in Ca2+ homeostasis. Acute applications of simvastatin on human skeletal muscle fibers triggered a Ca2+ wave of intra-cellular Ca2+ that mostly originates from sarcoplasmic reticulum (SR) Ca2+-release. In addition, simvastatin increased mitochondrial NADH content and induced mitochondrial membrane depolarization (EC50 = 1.96 μM) suggesting an altered mitochondrial function. Consequently on simvastatin application, a weak mitochondrial Ca2+ efflux (EC50 = 7.8μM) through permeability transient pore and Na+/Ca2+ exchanger was triggered, preceding the large SR-Ca2+ release. Increased SR Ca2+ content after acute application of statin is also suggested by the increased Ca2+ spark amplitude and by the effect of cyclopiazonic acid. We thus conclude that simvastatin induced alterations in mitochondrial function which lead to an increase in cytoplasmic Ca2+, SR-Ca2+ overload, and Ca2+ waves. Taken together, these statin-induced muscle dysregulations may contribute to myotoxicity. 相似文献
6.
Mitochondrial calcium channels 总被引:1,自引:0,他引:1
Uta C. Hoppe 《FEBS letters》2010,584(10):1975-1981
Mitochondrial Ca2+ handling plays an important role in energy production and various cellular signaling processes. Mitochondrial Ca2+ uptake is regulated by the mitochondrial Ca2+ uniporter (MCU), at least one non-MCU Ca2+ channel and possibly a mitochondrial ryanodine receptor. Two distinct mechanisms mediate Ca2+ outward transport, the Na+-dependent (mNCX) and the Na+-independent Ca2+ efflux. In recent years we gained more insight into the regulation and function of these different Ca2+ transport mechanisms. However, the precise physiological role and the molecular structure of all mitochondrial Ca2+ transporters and channels still has to be determined. 相似文献
7.
Mironova GD Belosludtsev KN Belosludtseva NV Gritsenko EN Khodorov BI Saris NE 《Journal of bioenergetics and biomembranes》2007,39(2):167-174
Earlier we found that in isolated rat liver mitochondria the reversible opening of the mitochondrial cyclosporin A-insensitive
pore induced by low concentrations of palmitic acid (Pal) plus Ca2+ results in the brief loss of Δψ [Mironova et al., J Bioenerg Biomembr (2004), 36:171–178]. Now we report that Pal and Ca2+, increased to 30 and 70 nmol/mg protein respectively, induce a stable and prolonged (10 min) partial depolarization of the
mitochondrial membrane, the release of Ca2+ and the swelling of mitochondria. Inhibitors of the Ca2+ uniporter, ruthenium red and La3+, as well as EGTA added in 10 min after the Pal/Ca2+-activated pore opening, prevent the release of Ca2+ and repolarize the membrane to initial level. Similar effects can be observed in the absence of exogeneous Pal, upon mitochondria
accumulating high [Sr2+], which leads to the activation of phospholipase A2 and appearance of endogenous fatty acids. The paper proposes a new model of the mitochondrial Ca2+ cycle, in which Ca2+ uptake is mediated by the Ca2+ uniporter and Ca2+ efflux occurs via a short-living Pal/Ca2+-activated pore. 相似文献
8.
Ca(2+) plays a central role in energy supply and demand matching in cardiomyocytes by transmitting changes in excitation-contraction coupling to mitochondrial oxidative phosphorylation. Matrix Ca(2+) is controlled primarily by the mitochondrial Ca(2+) uniporter and the mitochondrial Na(+)/Ca(2+) exchanger, influencing NADH production through Ca(2+)-sensitive dehydrogenases in the Krebs cycle. In addition to the well-accepted role of the Ca(2+)-triggered mitochondrial permeability transition pore in cell death, it has been proposed that the permeability transition pore might also contribute to physiological mitochondrial Ca(2+) release. Here we selectively measure Ca(2+) influx rate through the mitochondrial Ca(2+) uniporter and Ca(2+) efflux rates through Na(+)-dependent and Na(+)-independent pathways in isolated guinea pig heart mitochondria in the presence or absence of inhibitors of mitochondrial Na(+)/Ca(2+) exchanger (CGP 37157) or the permeability transition pore (cyclosporine A). cyclosporine A suppressed the negative bioenergetic consequences (ΔΨ(m) loss, Ca(2+) release, NADH oxidation, swelling) of high extramitochondrial Ca(2+) additions, allowing mitochondria to tolerate total mitochondrial Ca(2+) loads of >400nmol/mg protein. For Ca(2+) pulses up to 15μM, Na(+)-independent Ca(2+) efflux through the permeability transition pore accounted for ~5% of the total Ca(2+) efflux rate compared to that mediated by the mitochondrial Na(+)/Ca(2+) exchanger (in 5mM Na(+)). Unexpectedly, we also observed that cyclosporine A inhibited mitochondrial Na(+)/Ca(2+) exchanger-mediated Ca(2+) efflux at higher concentrations (IC(50)=2μM) than those required to inhibit the permeability transition pore, with a maximal inhibition of ~40% at 10μM cyclosporine A, while having no effect on the mitochondrial Ca(2+) uniporter. The results suggest a possible alternative mechanism by which cyclosporine A could affect mitochondrial Ca(2+) load in cardiomyocytes, potentially explaining the paradoxical toxic effects of cyclosporine A at high concentrations. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. 相似文献
9.
Marianne S. Jurkowitz Gerald P. Brierley 《Journal of bioenergetics and biomembranes》1982,14(5-6):435-449
A rapid loss of accumulated Ca2+ is produced by addition of H+ to isolated heart mitochondria. The H+-dependent Ca+ efflux requires that either (a) the NAD(P)H pool of the mitochondrion be oxidized, or (b) the endogenous adenine nucleotides be depleted. The loss of Ca2+ is accompanied by swelling and loss of endogenous Mg2–. The rate of H+-dependent Ca2+ efflux depends on the amount of Ca2+ and Pi taken up and the extent of the pH drop imposed. In the absence of ruthenium red the H+-induced Ca2+-efflux is partially offset by a spontaneous re-accumulation of released Ca2+. The H+-induced Ca2+ efflux is inhibited when the Pi transporter is blocked withN-ethylmaleimide, is strongly opposed by oligomycin and exogenous adenine nucleotides (particularly ADP), and inhibited by nupercaine. The H+-dependent Ca2+ efflux is decreased markedly when Na+ replaces the K+ of the suspending medium or when the exogenous K+/H+ exchanger nigericin is present. These results suggest that the H+-dependent loss of accumulated Ca2+ results from relatively nonspecific changes in membrane permeability and is not a reflection of a Ca2+/H+ exchange reaction. 相似文献
10.
Prooxidants induce release of Ca2+ from mitochondria through the giant solute pore in the mitochondrial inner membrane. However, under appropriate conditions prooxidants can induce Ca2+ release without inducing a nonspecific permeability change. Prooxidant-induced release of Ca2+ isselective. Presumably, this is the result of the operation of a permeability pathway for H+ coupled to the reversal of the Ca2+ uniporter, the latter generating the selectivity. The solute pore and prooxidant-induced Ca2+-specific pathways exhibit common sensitivities to a set of inhibitors and activators. It is proposed that the pore can operate in two open states: (1) permeable to H+ only and (2) permeable to solutes of Mr<1500. Under some conditions, prooxidants induce the H+-selective state which, in turn, collapses the inner membrane potential and permits selective loss of Ca2+ via the Ca2+ uniporter. 相似文献
11.
K. R. Robinson 《Planta》1977,136(2):153-158
The effect of external calcium and sodium ion concentrations on the calcium fluxes on the Pelvetia fastigiata De Toni egg was measured. Decreasing external [Ca2+] greatly increased the permeability of the eggs to Ca2+; at 1 mM external Ca2+ this permeability was 60 times as great as it was at the normal [Ca2+] of 10 mM. Lowering the external [Na+] also increased Ca2+ influx; at 2 mM Na+, the Ca2+ influx was 2–3 times as great as it was at the normal [Na+] if choline was used as a Na+ substitute. Lithium was less effective as a Na+ substitute in increasing Ca2+ influx. The extra Ca2+ influx in low [Na+] seemed to be dependent on internal [Na+]. The Ca2+ efflux increased transiently and then declined in low Na+ media. 相似文献
12.
线粒体和细胞内钙自稳平衡 总被引:10,自引:0,他引:10
线粒体对胞浆钙信号调节作用的研究已经历较长时间.近年,随着研究方法和技术的不断改进,发现在绝大多数生理条件下,线粒体都能参与胞内钙通信过程.线粒体可感受其周围钙微区的存在从而摄取钙,又可以通过钠-钙交换和大分子孔道将钙释放出来,因此可以调节胞浆钙信号的时空特性,影响相关的细胞功能.但是,由于技术上的局限性,目前的研究仍然存在模糊不清和自相矛盾之处,有待于进一步研究. 相似文献
13.
Chinopoulos C Starkov AA Grigoriev S Dejean LM Kinnally KW Liu X Ambudkar IS Fiskum G 《Journal of bioenergetics and biomembranes》2005,37(4):237-247
Mitochondria contribute to cytosolic Ca2+ homeostasis through several uptake and release pathways. Here we report that 1,2-sn-diacylglycerols (DAGs) induce Ca2+ release from Ca2+-loaded mammalian mitochondria. Release is not mediated by the uniporter or the Na+/Ca2+ exchanger, nor is it attributed to putative catabolites. DAGs-induced Ca2+ efflux is biphasic. Initial release is rapid and transient, insensitive to permeability transition inhibitors, and not accompanied by mitochondrial swelling. Following initial rapid release of Ca2+ and relatively slow reuptake, a secondary progressive release of Ca2+ occurs, associated with swelling, and mitigated by permeability transition inhibitors. The initial peak of DAGs-induced Ca2+ efflux is abolished by La3+ (1 mM) and potentiated by protein kinase C inhibitors. Phorbol esters, 1,3-diacylglycerols and 1-monoacylglycerols do not induce mitochondrial Ca2+ efflux. Ca2+-loaded mitoplasts devoid of outer mitochondrial membrane also exhibit DAGs-induced Ca2+ release, indicating that this mechanism resides at the inner mitochondrial membrane. Patch clamping brain mitoplasts reveal DAGs-induced slightly cation-selective channel activity that is insensitive to bongkrekic acid and abolished by La3+. The presence of a second messenger-sensitive Ca2+ release mechanism in mitochondria could have an important impact on intracellular Ca2+ homeostasis. 相似文献
14.
E. I. Khoroshavina M. V. Dubinin A. V. Khokhlov V. N. Samartsev 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2018,12(2):128-136
The effect of bile acids as inducers of Ca2+ efflux from the matrix was studied on isolated rat liver mitochondria. Mitochondria in the presence of cyclosporin A (CsA) were energized by succinate, then loaded with Ca2+ and after the addition of the calcium uniporter inhibitor ruthenium red were de-energized by malonate. It was shown that under these conditions hydrophobic bile acids lithocholic and chenodeoxycholic at concentrations of 10 and 30 μM respectively and hydrophilic bile acids ursodeoxycholic and cholic at a concentration of 400 μM induce Ca2+ efflux from the mitochondrial matrix. It is noted that the efflux of these ions is not associated with damage of the inner mitochondrial membrane by bile acids, since it is accompanied by the generation of Δψ, i.e., the formation of the diffusion potential. It is assumed that along with induction of calcium efflux from the matrix, bile acids are also capable of transporting hydrogen and potassium ions in the opposite direction, i.e., perform H+/Ca2+ and K+/Ca2+ exchange. It was found that ruthenium red added to Ca2+-loaded energized mitochondria prevents the return of these ions to the matrix and weakens the effect of chenodeoxycholic acid as an inducer of the CsA-sensitive mitochondrial pore and the effect of ursodeoxycholic acid as an inducer of CsA-insensitive permeability of the inner mitochondrial membrane. We conclude that in the conditions of the calcium uniporter activity decrease, Ca2+ efflux from the matrix induced by bile acids can be considered as one of the mechanisms reducing their effectiveness as inducers of the Ca2+-dependent CsA-sensitive pore and CsA-insensitive permeability transition in mitochondria. 相似文献
15.
16.
Two types of Na+-independent Mg2+ efflux exist in erythrocytes: (1) Mg2+ efflux in sucrose medium and (2) Mg2+ efflux in high Cl− media such as KCl-, LiCl- or choline Cl-medium. The mechanism of Na+-independent Mg2+ efflux in choline Cl medium was investigated in this study. Non-selective transport by the following transport mechanisms has been excluded: K+,Cl−- and Na+,K+,Cl−-symport, Na+/H+-, Na+/Mg2+-, Na+/Ca2+- and K+(Na+)/H+ antiport, Ca2+-activated K+ channel and Mg2+ leak flux. We suggest that, in choline Cl medium, Na+-independent Mg2+ efflux can be performed by non-selective transport via the choline exchanger. This was supported through inhibition of Mg2+ efflux by hemicholinum-3 (HC-3), dodecyltrimethylammonium bromide (DoTMA) and cinchona alkaloids, which are inhibitors of the choline exchanger. Increasing concentrations of HC-3 inhibited the efflux of choline and efflux of Mg2+ to the same degree. The Kd value for inhibition of [14C]choline efflux and for inhibition of Mg2+ efflux by HC-3 were the same within the experimental error. Inhibition of choline efflux and of Mg2+ efflux in choline medium occurred as follows: quinine>cinchonine>HC-3>DoTMA. Mg2+ efflux was reduced to the same degree by these inhibitors as was the [14C]choline efflux. 相似文献
17.
The mitochondrial permeability transition pore (mPTP) has long been known to have a role in mitochondrial calcium (Ca2+) homeostasis under pathological conditions as a mediator of the mitochondrial permeability transition and the activation of the consequent cell death mechanism. However, its role in the context of mitochondrial Ca2+ homeostasis is not yet clear. Several studies that were based on PPIF inhibition or knock out suggested that mPTP is involved in the Ca2+ efflux mechanism, while other observations have revealed the opposite result. 相似文献
18.
Mitochondria modulate cellular Ca2+ signals by accumulating the ion via a uniporter and releasing it via Na+- or H+-exchange. In smooth muscle, inhibition of mitochondrial Ca2+ uptake inhibits Ca2+ release from the sarcoplasmic reticulum (SR) via inositol-1,4,5-trisphosphate-sensitive receptors (IP3R). At least two mechanisms may explain this effect. First, localised uptake of Ca2+ by mitochondria may prevent negative feedback by cytosolic Ca2+ on IP3R activity, or secondly localised provision of Ca2+ by mitochondrial efflux may maintain IP3R function or SR Ca2+ content. To distinguish between these possibilities the role of mitochondrial Ca2+ efflux on IP3R function was examined. IP3 was liberated in freshly isolated single colonic smooth muscle cells and mitochondrial Na+–Ca2+ exchanger inhibited with CGP-37157 (10 μM). Mitochondria accumulated Ca2+ during IP3-evoked [Ca2+]c rises and released the ion back to the cytosol (within 15 s) when mitochondrial Ca2+ efflux was active. When mitochondrial Ca2+ efflux was inhibited by CGP-37157, an extensive and sustained loading of mitochondria with Ca2+ occurred after IP3-evoked Ca2+ release. IP3-evoked [Ca2+]c rises were initially unaffected, then only slowly inhibited by CGP-37157. IP3R activity was required for inhibition to occur; incubation with CGP-37157 for the same duration without IP3 release did not inhibit IP3R. CGP-37157 directly inhibited voltage-gated Ca2+ channel activity, however SR Ca2+ content was unaltered by the drug. Thus, the gradual decline of IP3R function that followed mitochondrial Na+–Ca2+ exchanger inhibition resulted from a gradual overload of mitochondria with Ca2+, leading to a reduced capacity for Ca2+ uptake. Localised uptake of Ca2+ by mitochondria, rather than mitochondrial Ca2+ efflux, appears critical for maintaining IP3R activity. 相似文献
19.
Shmuel Muallem Timothy Beeker Stephen J. Pandol 《The Journal of membrane biology》1988,102(2):153-162
Summary The relative contributions of the Na+/Ca2+ exchange and the plasma membrane Ca2+ pump to active Ca2+ efflux from stimulated rat pancreatic acini were studied. Na+ gradients across the plasma membrane were manipulated by loading the cells with Na+ or suspending the cells in Na+-free media. The rates of Ca2+ efflux were estimated from measurements of [Ca2+]
i
using the Ca2+-sensitive fluorescent dye Fura 2 and45Ca efflux. During the first 3 min of cell stimulation, the pattern of Ca2+ efflux is described by a single exponential function under control, Na+-loaded, and Na+-depleted conditions. Manipulation of Na+ gradients had no effect on the hormone-induced increase in [Ca2+]
i
. The results indicate that Ca2+ efflux from stimulated pancreatic acinar cells is mediated by the plasma membrane Ca2+ pump. The effects of several cations, which were used to substitute for Na+, on cellular activity were also studied. Choline+ and tetramethylammonium+ (TMA+) released Ca2+ from intracellular stores of pancreatic acinar, gastric parietal and peptic cells. These cations also stimulated enzyme and acid secretion from the cells. All effects of these cations were blocked by atropine. Measurements of cholecystokinin-octapeptide (CCK-OP)-stimulated amylase release from pancreatic acini, suspended in Na+, TMA+, choline+, or N-methyl-d-glucamine+ (NMG+) media containing atropine, were used to evaluate the effect of the cations on cellular function. NMG+, choline+, and TMA+ inhibited amylase release by 55, 40 and 14%, respectively. NMG+ also increased the Ca2+ permeability of the plasma membrane. Thus, to study Na+ dependency of cellular function, TMA+ is the preferred cation to substitute for Na+. The stimulatory effect of TMA+ can be blocked by atropine. 相似文献
20.
Oxygen free radicals and calcium homeostasis in the heart 总被引:10,自引:0,他引:10
Masanori Kaneko Yuji Matsumoto Hideharu Hayashi Akira Kobayashi Noboru Yamazaki 《Molecular and cellular biochemistry》1994,135(1):99-108
Many experiments have been done to clarify the effects of oxygen free radicals on Ca2+ homeostasis in the hearts. A burst of oxygen free radicals occurs immediately after reperfusion, but we have to be reminded that the exact levels of oxygen free radicals in the hearts are yet unknown in both physiological and pathophysiological conditions. Therefore, we should give careful consideration to this point when we perform the experiments and analyze the results. It is, however, evident that Ca2+ overload occurs when the hearts are exposed to an excess amount of oxygen free radicals. Though ATP-independent Ca2+ binding is increased, Ca2+ influx through Ca2+ channel does not increase in the presence of oxygen free radicals. Another possible pathway through which Ca2+ can enter the myocytes is Na+?Ca2+ exchanger. Although, the activities of Na+?K+ ATPase and Na+?H+ exchange are inhibited by oxygen free radicals, it is not known whether intracellular Na+ level increases under oxidative stress or not. The question has to be solved for the understanding of the importance of Na+?Ca2+ exchange in Ca2+ influx process from extracellular space. Another question is ‘which way does Na+?Ca2+ exchange work under oxidative stress? Net influx or efflux of Ca2+?’ Membrane permeability for Ca2+ may be maintained in a relatively early phase of free radical injury. Since sarcolemmal Ca2+-pump ATPase activity is depressed by oxygen free radicals, Ca2+ extrusion from cytosol to extracellular space is considered to be reduced. It has also been shown that oxygen free radicals promote Ca2+ release from sarcoplasmic reticulum and inhibit Ca2+ sequestration to sarcoplasmic reticulum. Thus, these changes in Ca2+ handling systems could cause the Ca2+ overload due to oxygen free radicals. 相似文献