共查询到20条相似文献,搜索用时 15 毫秒
1.
S W Rabkin 《Experimental cell research》1990,188(2):262-266
The purpose of this study was to examine the effect of epidermal growth factor (EGF) on cardiac function and to explore ionic mechanisms as potential explanations for EGF-induced changes in cardiac contractile frequency. Cardiac cell aggregates were prepared from 7-day-old chick embryo hearts and were maintained in culture. EGF over a concentration range of 5 to 20 ng/ml produced a dose-dependent increase in cardiac contractile frequency. Inhibition of Na(+)-H+ exchange by amiloride antagonized the action of EGF. Inhibition of Na(+)-Ca2+ exchange by dichlorobenzamil prevented the effects of EGF. Inhibition of voltage-dependent calcium influx by diltiazem also antagonized the effect of EGF. The positive chronotropic action of EGF was significantly enhanced when the concentration of Na+ or Ca2+ was increased in the medium. These data indicate that EGF has a definite dose-dependent effect on the cardiac contractile frequency that is operative through ionic transport mechanisms that include increased calcium entry through voltage-dependent calcium channels and stimulation of Na(+)-H+ and Na(+)-Ca2+ exchange. The similarity in the effects of inhibition of these three ionic mechanisms suggests they are interrelated so that interference at any step in the process inhibits the action of EGF on cardiac myocytes. 相似文献
2.
The role of intracellular Ca2+ as essential activator of the Na+---Ca2+ exchange carrier was explored in membrane vesicles containing 67% right-side-out and 10% inside-out vesicles, isolated from squid optic nerves. Vesicles containing 100 μM free calcium exhibited a 2-fold increase in the initial rate of Nai+-dependent Ca2+ uptake as compared with vesicles where intravesicular calcium was chelated by 2 mM EGTA or 10 mM HEDTA. The activatory effect exerted by intravesicular Ca2+ on the reverse mode of Na+---Ca2+ exchange (i.e. Nai+---Ca02+ exchange) is saturated at about 100 μM Cai2+ and displays an apparent K1/2 of 12 μM. Intravesicular Ca2+ produced activation of Nai+---Ca02+ exchange activity rather than an increase in Ca2+ uptake due to Ca2+---Ca2+ exchange. The presence of Cai2+ was essential for the Nai+-dependent Na+ influx, a partial reaction of the Na+---Ca2+ exchanger. In fact, the Na+ influx levels in vesicles loaded with 2 mM EGTA were close to those expected from diffusional leak while in vesicles containing Cai2+ an additional Na+---Na+ exchange was measured. The results suggest that in nerve membrane vesicles Ca2+ at the inner aspect of the membrane acts as an activator of the Na+---Ca2+ exchange system. 相似文献
3.
In this study we prepared sarcolemmal fractions from bovine and rat hearts; their Na+K+ ATPase activities, measured in the presence of saponin to unmask latent Na+K+ ATPase, were 59.4 and 48.8 µ mol Pi/mg protein · h, respectively. The rate of Na+dependent Ca2+ uptake was linear for the first 10 s and a plateau was reached in 3 min. Oxidation by free radical generation either with H2O2, FeSO4 plus DTT or xanthine oxidase plus hypoxanthine stimulated Na+/Ca2+ exchange in a time-dependent manner. The stimulation was abolished by deferoxamine or o-phenanthroline. By contrast, oxidation by HOCI inhibited Na+/Ca2+ exchange in proportion to its concentration, and this inhibition was antagonized by DTT. DTT alone had no effect on the exchange. Insulin stimulated Na+/Ca2+ exchange, its maximal effect was attained after 30min incubation with 100 µ units/ml. N-ethylmaleimide inhibited the exchange both in the presence and in the absence of insulin. Sarcolemmal fractions prepared from hearts of alloxan-treated, acutely diabetic rats showed a significant decrease in Na+/Ca2+ exchange. Addition of insulin in vitro significantly stimulated Na+/Ca2+ exchange of both diabetic and control groups. The results indicate that sarcolemmal Na+/Ca2+ exchange function is modulated by oxidation-reduction states and by the presence of insulin. 相似文献
4.
He-Ping Meng Michael J. B. Kutryk Grant N. Pierce 《Molecular and cellular biochemistry》1990,92(1):45-51
Summary The effects of platelet-activating factor (PAF) on Na+-dependent calcium uptake in myocardial sarcolemmal vesicles were examined in order to clarify its mechanism of inotropic action on the heart. PAF (40 and 20 µM) significantly inhibited Na+-Ca2+ exchange by 61% and 37%, respectively. Both initial rate of exchange and maximal exchange were inhibited. The Km for the reaction was not altered but Vmax was lowered 55% by PAF. Lyso-PAF inhibited Na+-Ca2+ exchange to a similar degree as PAF. CV-3988, a specific PAF receptor antagonist, failed to diminish the inhibitory effect of PAF on Na+-Ca2+ exchange, suggesting that the effect of PAF on Na+-Ca 2+ exchange is not via a receptor mechanism. The passive permeability of sarcolemmal vesicles to Ca2+ was markedly elevated after PAF treatment. However, this effect could not account for the decrease in Na+-Ca2+ exchange. Interestingly, passive Ca2+ binding to cardiac sarcolemma was increased by 40 µM PAF. This study indicates that a depression of Na+-Ca2+ exchange probably does not play a role in the negative inotropic effect of PAF on the myocardium under physiological conditions. Its mechanism of action on Na+-Ca2+ exchange is discussed. 相似文献
5.
Alexander V. Zhdanov Manus W. Ward Ekaterina A. Souslova Jochen H.M. Prehn 《BBA》2010,1797(9):1627-1637
Fluctuating extracellular Ca2+ regulates many aspects of neuronal (patho)physiology including cell metabolism and respiration. Using fluorescence-based intracellular oxygen sensing technique, we demonstrate that depletion of extracellular Ca2+ from 1.8 to ≤ 0.6 mM by chelation with EGTA induces a marked spike in O2 consumption in differentiated PC12 cells. This respiratory response is associated with the reduction in cytosolic and mitochondrial Ca2+, minor depolarization on the mitochondrial membrane, moderate depolarization of plasma membrane, and no changes in NAD(P)H and ATP. The response is linked to the influx of extracellular Na+ and the subsequent activation of mitochondrial Na+/Ca2+ and Na+/H+ exchange. The mitochondrial Na+/Ca2+ exchanger (mNCX) activated by Na+ influx reduces Ca2+ and increases Na+ levels in the mitochondrial matrix. The excess of Na+ activates the mitochondrial Na+/H+ exchanger (NHE) increasing the outward pumping of protons, electron transport and O2 consumption. Reduction in extracellular Na+ and inhibition of Na+ influx through the receptor operated calcium channels and plasmalemmal NHE reduce the respiratory response. Inhibition of the mNCX, L-type voltage gated Ca2+ channels or the release of Ca2+ from the endoplasmic reticulum also reduces the respiratory spike, indicating that unimpaired intercompartmental Ca2+ exchange is critical for response development. 相似文献
6.
Grant N. Pierce 《Molecular and cellular biochemistry》1987,78(1):89-94
Na+-H+ exchange and passive Na+ flux were investigated in cardiac sarcolemmal vesicles as a function of changing the ionic composition of the reaction media. The inclusion of EGTA in the reaction medium resulted in a potent stumulation of Na+ uptake by Na+-H+ exchange. It was found that millimolar concentrations of Mg2+ and Li+ were capable of inhibiting Na+-H+ exchange by 80%. One mechanism by which these ions may inhibit intravesicular Na+ accumulation by Na+-H+ exchange is via an increase in Na+ efflux. An examination of Na+ efflux kinetics from vesicles pre-loaded with Na+ revealed that Na+, Ca2+, Mg2+ and Li+ could stimulate Na+ efflux. Na+-H+ exchange was potently inhibited by an organic divalent cation, dimenthonium, which screens membrane surface charge. This would suggest that Na+-H+ exchange occurs in the diffuse double layer region of cardiac sarcolemma and this phenomenon is distinctly different from other Na+ transport processes. The results in this study indicate that in addition to a stimulation of Na+ efflux, the inhibitory effects of Mg2+, Ca2+ and Li+ on Na+-H+ exchange may also involve a charge dependent screening of Na+ interactions with the membrane. 相似文献
7.
The Na+/Ca2+ antiporter was purified from beef heart mitochondria and reconstituted into liposomes containing fluorescent probes selective for Na+ or Ca2+. Na+/Ca2+ exchange was strongly inhibited at alkaline pH, a property that is relevant to rapid Ca2+ oscillations in mitochondria. The effect of pH was mediated entirely via an effect on the Km for Ca2+. When present on the same side as Ca2+, K+ activated exchange by lowering the Km for Ca2+ from 2 to 0.9 μM. The Km for Na+ was 8 mM. In the absence of Ca2+, the exchanger catalyzed high rates of Na+/Li+ and Na+/K+ exchange. Diltiazem and tetraphenylphosphonium cation inhibited both Na+/Ca2+ and Na+/K+ exchange with IC50 values of 10 and 0.6 μM, respectively. The Vmax for Na+/Ca2+ exchange was increased about fourfold by bovine serum albumin, an effect that may reflect unmasking of an autoregulatory domain in the carrier protein. 相似文献
8.
Lynn R. Fraser 《Molecular reproduction and development》1993,36(3):368-376
The sequence of ionic changes involved in initiation of acrosomal exocytosis in capacitated mouse spermatozoa was investigated. Earlier studies demonstrated that a large influx of Na+ is required for exocytosis, this Na+ apparently being associated with an increase in intracellular pH (pHi) via an Na+-H+ exchanger. This rise in pHi may in turn activate calcium channels and permit the influx of extracellular Ca2+ needed to trigger acrosomal exocytosis. In the present study, the dihydropyridine voltage-dependent calcium channel antagonist nifedipine was able to inhibit significantly exocytosis in sperm cells treated in various ways capable of stimulating acrosomal loss. The monovalent cation ionophore monensin can promote Na+ entry required for both capacitation and acrosomal exocytosis, as demonstrated by using chlortetracycline to monitor changes in sperm functional potential. In the presence of 10 nM nifedipine, monensin treatment accelerated capacitation but was unable to trigger exocytosis. The requirement for internalization of a high concentration of Na+ can be bypassed by the addition of 25 mM NH4CI to raise the pHi of cells capacitated in 25NH4CI to raise the pHi of cells capacitated in 25 mM Na+ (insufficient Na+ to support exocytosis under usual conditions). Again, introduction of nifedipine was able to inhibit exocytosis. In a third experimental approach, amiloridestimulated exocytosis in capacitated cells was significantly inhibited by nifedipine. In contrast to these treatments directed at specific mechanisms, the ability of the Ca2+ inophore A23187 to promote more general entry of Ca2+ and thereby to accelerate capacitation and exocytosis was not inhibited by nifedipine. Finally, monensin-treated cells exhibited a rise and then a fall in 45Ca2+ uptake, the time course of which paralleled stimulation of acrosomal exocytosis in similarly treated cells. Nifedipine significantly reduced this uptake. The fact that nifedipine can block exocytosis induced by a variety treatments strongly suggests that voltage-dependent calcium channels play a pivotal role in the response. These results are consistent with the following sequence of ionic changes in capacitated cells leading to acrosomal exocytosis: [Na+]i ↑ → [H]i↓ → pHi ↑ → activation of calcium channels → [Ca2+]i ↑ → exocytosis. Given that zona-induced exocytosis is reportedly an indirect response, mediated by voltage-dependent calcium channels, and that the Na+-H+ exchanger in somatic cells can be activated by receptor-mediated mechanisms, we suggest that sperm-zona inter action promotes an influx of Na+ by activating an Na+-H+ exchanger and thereby initiating the above sequence of changes. © 1993 Wiley-Liss, Inc. 相似文献
9.
《Cell calcium》2008,43(6):606-617
We have previously demonstrated a role for the reorganization of the actin cytoskeleton in store-operated calcium entry (SOCE) in human platelets and interpreted this as evidence for a de novo conformational coupling step in SOCE activation involving the type II IP3 receptor and the platelet hTRPC1-containing store-operated channel (SOC). Here, we present evidence challenging this model. The actin polymerization inhibitors cytochalasin D or latrunculin A significantly reduced Ca2+ but not Mn2+ or Na+ entry into thapsigargin (TG)-treated platelets. Jasplakinolide, which induces actin polymerization, also inhibited Ca2+ but not Mn2+ or Na+ entry. However, an anti-hTRPC1 antibody inhibited TG-evoked entry of all three cations, indicating that they all permeate an hTRPC1-containing store-operated channel (SOC). These results indicate that the reorganization of the actin cytoskeleton is not involved in SOC activation. The inhibitors of the Na+/Ca2+ exchanger (NCX), KB-R7943 or SN-6, caused a dose-dependent inhibition of Ca2+ but not Mn2+ or Na+ entry into TG-treated platelets. The effects of the NCX inhibitors were not additive with those of actin polymerization inhibitors, suggesting a common point of action. These results indicate a role for two Ca2+ permeable pathways activated following Ca2+ store depletion in human platelets: A Ca2+-permeable, hTRPC1-containing SOC and reverse Na+/Ca2+ exchange, which is activated following Na+ entry through the SOC and requires a functional actin cytoskeleton. 相似文献
10.
Tomoji Hata Naoki Makino Hironobu Nakanishi Takashi Yanaga 《Molecular and cellular biochemistry》1988,84(1):65-76
Summary The purpose of this study was to examine the effect of three classes of Ca2+ antagonists, diltiazem, verapamil and nifedipine on Na+-Ca2+ exchange mechanism in the sarcolemmal vesicles isolated from canine heart. Na+-Ca2+ exchange and Ca2+ pump (ATP-dependent Ca2+ uptake) activities were assessed using the Millipore filtration technique. sarcolemmal vesicles used in this study are estimated to consist of several subpopulations wherein 23% are inside-out and 55% are right side-out sealed vesicles in orientation. The affect of each Ca2+ antagonist on the Na+-dependent Ca2+ uptake was studied in the total population of sarcolemmal vesicles, in which none of the agents depressed the initial rate of Ca2+ uptake until concentrations of 10 M were incubated in the incubation medium. However, when sarcolemmal vesicles were preloaded with Ca2+ via ATP-dependent Ca2+ uptake, cellular Ca2+ influx was depressed only by verapamil (28%) at 1 M in the efflux medium with 8 mM Na+. Furthermore, inhibition of Ca2+ efflux by verapamil was more pronounced in the presence of 16 mM Na+ in the efflux medium. The order of inhibition was; verapamil > diltiazem > nifedipine. These results indicate that same forms of Ca2+-antagonist drugs may affect the Na+-Ca2+ exchange mechanism in the cardiac sarcolemmal vesicles and therefore we suggest this site of action may contribute to their effects on the myocardium. 相似文献
11.
The effects of a new, potent, and selective inhibitor of the Na+/Ca2+ exchange, SEA-0400 (SEA), on steady-state outward (forward exchange), inward (reverse exchange), and Ca2+/Ca2+ transport exchange modes were studied in internally dialyzed squid giant axons from both the extra- and intracellular sides. Inhibition by SEA takes place preferentially from the intracellular side of the membrane. Its inhibition has the following characteristics: it increases synergic intracellular Na+ (Nai+) + intracellular H+ (Hi+) inactivation, is antagonized by ATP and intracellular alkalinization, and is enhanced by intracellular acidification even in the absence of Na+. Inhibition by SEA is still present even after 1 h of its removal from the experimental solutions, whereas removal of the cointeracting agents of inhibition, Nai+ and Hi+, even in the continuous presence of SEA, releases inhibition, indicating that SEA facilitates the reversible attachment of the natural Hi+ and Nai+ synergic inhibitors. On the basis of a recent model of squid Na+/Ca2+ exchange regulation (DiPolo R and Beaugé L. J Physiol 539: 791803, 2002), we suggest that SEA acts on the Hi+ + Nai+ inactivation process and can interact with the Na+-free and Na+-bound protonized carrier. Protection by ATP concurs with the antagonism of the nucleotide by Hi+ + Nai+ synergic inhibition. ionic-metabolic interactions 相似文献
12.
Summary The Ca2+ permeability of rabbit skeletal muscle sarcolemmal vesicles was investigated by means of radioisotope flux measurements. A membrane vesicle fraction highly enriched in sarcolemma, as revealed by enzymatic markers, was obtained from the 22–27% region of sucrose gradients after isopycnic centrifugation. The ability of sarcolemmal vesicles to exchange Na+ for Ca2+ was investigated by measuring Ca2+ influx into and efflux from sarcolemmal vesicles in the presence and absence of a Na+ gradient. It was found that Ca2+ movements were enhanced in the direction of the higher Na+ concentration. When intra- and extravesicular Na+ concentrations were high, Na+–Na+ exchange predominated and Na+–Ca2+ exchange was low or absent. The presence of the Ca2+ ionophore A23187 in the dilution medium resulted in the rapid release of Ca2+ and the elimination of the Na+-enhanced efflux of Ca2+, suggesting that internal rather than bound external Ca2+ was exchanged with Na+. La3+ abolished Na+–Ca2+ exchange and decreased overall membrane permeability. Na+–Ca2+ exchange was not due to sarcoplasmic reticulum or mitochondrial contaminants. This investigation suggests that skeletal muscle, like cardiac muscle and neurons, is capable of a transmembranous Na+–Ca2+ exchange. 相似文献
13.
Lysophosphatidylcholine (LPC) has been reported to stimulate Na+-H+ exchange in rat cardiomyocytes. This action may be important in pathological conditions like ischemic injury where LPC is generated and Na+-H+ exchange activation is an important determinant of cardiac damage and dysfunction. It is unclear, however, if this stimulation of Na+-H+ exchange by LPC occurs through a direct action on the exchanger or through stimulation of a second messenger pathway. The purpose of the present investigation was to determine if lysolipids could directly affect Na+-H+ exchange. Purified cardiac sarcolemmal membranes were isolated and Na+-H+ exchange was measured by radioisotopic methods following addition of LPC. There were no effects of LPC on Na+-H+ exchange at LPC concentrations of 100 M at all reaction times examined. Lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), lysophosphatidylinositol (LPI) and lysoplasmenylcholine (LPEC) also did not alter Na+-H+ exchange at all concentrations and reaction times examined. We conclude that any stimulatory effects of lysolipids on Na+-H+ exchange do not occur through a direct action on the exchanger or its membrane lipid environment and must occur through a second messenger pathway. 相似文献
14.
Walter F. Riker Jr. Michiko Okamoto Joseph F. Artusio Jr. 《Neurochemical research》1990,15(4):457-465
Cat soleus motor nerve terminals, after high frequency conditioning, generate a post-tetanic repetition (PTR) which leads to a post-tetanic (PTP) of the muscle response. This property enables quantitative assessment of enhancement or depression of this nerve terminal excitability in vivo. The present study focuses on ionic mechanisms underlying the PTRs produced in this neuromuscular system either by high frequency stimulation or edrophonium. Ouabain was used as a specific probe for inhibition of Na+–K+ ATPase and its known consequences on Na+ and Ca2+ translocation. Ouabain pretreatment doubled the duration over which single stimuli, following either high frequency or edrophonium conditioning produced PTR. Ouabain in the doses used had no effectper se but as a function of dose augmented the frequency dependent responses. This pointed to Na+ loading of nerve terminals via high frequency stimulation plus ouabain inhibition of Na+–K+ ATPase. Ouabain potentiation of PTR responses evidently depends on exchange of intra-terminal sodium for external calcium. Thus, calcium entry blockers, Mn2+, and Co2+ suppressed or abolished the potentiations both before and after ouabain. Diphenylhydantoin, a Na+ and Ca2+ blocker, acted similarly. The effects of stimulation frequency, ouabain and the sequence of events leading to PTR in the soleus neuromuscular system appeared in general no different from those derived from the many in vitro microphysiologic studies of this phenomenon. Thus, EPPs were augmented and prolonged. It was concluded that intracellular Ca2+ is critical for regulating the stability of systems in which repetitive firing is both a normal and abnormal function.Special issue dedicated to Dr. Sidney Udenfriend 相似文献
15.
Naranjan S. Dhalla Vincenzo Panagia Naoki Makino Robert E. Beamish 《Molecular and cellular biochemistry》1988,82(1-2):75-79
In order to identify defects in Na+-Ca2+ exchange and Ca2+-pump systems in cardiomyopathic hearts, the activities of sarcolemmal Na+-dependent Ca2+ uptake, Na+-induced Ca2+ release, ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase were examined by employing cardiomyopathic hamsters (UM-X7.1) and catecholamine-induced cardiomyopathy produced by injecting isoproterenol into rats. The rates of Na+-dependent Ca2+ uptake, ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase activities of sarcolemmal vesicles from genetically-linked cardiomyopathic as well as catecholamine-induced cardiomyopathic hearts were decreased without any changes in Na+-induced Ca2+-release. Similar results were obtained in Ca2+-paradox when isolated rat hearts were perfused for 5 min with a medium containing 1.25 mM Ca2+ following a 5 min perfusion with Ca2+-free medium. Although a 2 min reperfusion of the Ca2+-free perfused hearts depressed sarcolemmal Ca2+-pump activities without any changes in Na+-induced Ca2+-release, Na+-dependent Ca2+ uptake was increased. These results indicate that alterations in the sarcolemmal Ca2+-efflux mechanisms may play an important role in cardiomyopathies associated with the development of intracellular Ca2+ overload. 相似文献
16.
《Channels (Austin, Tex.)》2013,7(6):457-462
NaV1.5 is a mechanosensitive voltage-gated Na+ channel encoded by the gene SCN5A, expressed in cardiac myocytes and required for phase 0 of the cardiac action potential (AP). In the cardiomyocyte, ranolazine inhibits depolarizing Na+ current and delayed rectifier (IKr) currents. Recently, ranolazine was also shown to be an inhibitor of NaV1.5 mechanosensitivity. Stretch also accelerates the firing frequency of the SA node, and fluid shear stress increases the beating rate of cultured cardiomyocytes in vitro. However, no cultured cell platform exists currently for examination of spontaneous electrical activity in response to mechanical stimulation. In the present study, flow of solution over atrial myocyte-derived HL-1 cultured cells was used to study shear stress mechanosensitivity of Na+ current and spontaneous, endogenous rhythmic action potentials. In voltage-clamped HL-1 cells, bath flow increased peak Na+ current by 14 ± 5%. In current-clamped cells, bath flow increased the frequency and decay rate of AP by 27 ± 12% and 18 ± 4%, respectively. Ranolazine blocked both responses to shear stress. This study suggests that cultured HL-1 cells are a viable in vitro model for detailed study of the effects of mechanical stimulation on spontaneous cardiac action potentials. Inhibition of the frequency and decay rate of action potentials in HL-1 cells are potential mechanisms behind the antiarrhythmic effect of ranolazine. 相似文献
17.
John P. Reeves 《Journal of bioenergetics and biomembranes》1998,30(2):151-160
The Na+/Ca2+ exchange system is the primary Ca2+ efflux mechanism in cardiac myocytes, and plays an important role in controlling the force of cardiac contraction. The exchanger protein contains 11 transmembrane segments plus a large hydrophilic domain between the 5th and 6th transmembrane segments; the transmembrane regions are reponsible for mediating ion translocation while the hydrophilic domain is responsible for regulation of activity. Exchange activity is regulated in vitro by interconversions between an active state and either of two inactive states. High concentrations of cytosolic Na+ or the absence of cytosolic Ca2+ promote the formation of the inactive states; phosphatidylinositol-(4,5)bisphosphate (or other negatively charged phospholipids) and cytosolic Ca2+ counteract the inactivation process. The importance of these mechanisms in regulating exchange activity under normal physiological conditions is uncertain. Exchanger function is also dependent upon cytoskeletal interactions, and the exchanger's location with respect to intracellular Ca2+-sequestering organelles. An understanding of the exchanger's function in normal cell physiology will require more detailed information on the proximity of the exchanger and other Ca2+-transporting proteins, their interactions with the cytoskeleton, and local concentrations of anionic phospholipids and transported ions. 相似文献
18.
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
19.
Ya. M. Shuba 《Neurophysiology》1997,29(4-5):227-232
The plasmalemmal Na+−Ca2+ exchanger is a coupled Na+ and Ca2+ transport mechanism that plays an important role in regulation of Ca2+ homeoslasis in many cell types. A robust Na+−Ca2+ exchange system is present in the heart where it comprises essential Ca2+ extrusion, as well as Ca2+ entry pathways, that significantly contribute to the maintenance of cardiac contractility. The review examines the basic
properties of Na+−Ca2+ exchange, the patterns of its regulation, as well as the latest achievements in the cloning and structure-function studies
of a Na+−Ca2+ exchanger molecule. 相似文献
20.
The changes in cardiac function caused by calcium overload are reviewed. Intracellular Ca2+ may increase in different structures [e.g. sarcoplasmic reticulum (SR), cytoplasm and mitochondria] to an excessive level which induces electrical and mechanical abnormalities in cardiac tissues. The electrical manifestations of Ca2+ overload include arrhythmias caused by oscillatory (Vos) and non-oscillatory (Vex) potentials. The mechanical manifestations include a decrease in force of contraction, contracture and aftercontractions. The underlying mechanisms involve a role of Na+ in electrical abnormalities as a charge carrier in the Na+-Ca2+ exchange and a role of Ca2+ in mechanical toxicity. Ca2+ overload may be induced by an increase in [Na+]i through the inhibition of the Na+-K+ pump (e.g. toxic concentrations of digitalis) or by an increase in Ca2+ load (e.g. catecholamines). The Ca2+ overload is enhanced by fast rates. Purkinje fibers are more susceptible to Ca2+ overload than myocardial fibers, possibly because of their greater Na+ load. If the SR is predominantly Ca2+ overloaded, Vos and fast discharge are induced through an oscillatory release of Ca2+ in diastole from the SR; if the cytoplasm is Ca2+ overloaded, the non-oscillatory Vex tail is induced at negative potentials. The decrease in contractile force by Ca2+ overload appears to be associated with a decrease in high energy phosphates, since it is enhanced by metabolic inhibitors and reduced by metabolic substrates. The ionic currents Ios and Iex underlie Vos and Vex, respectively, both being due to an electrogenic extrusion of Ca2+ through the Na+-Ca2+ exchange. Ios is an oscillatory current due to an oscillatory release of Ca2+ in early diastole from the Ca2+-overloaded SR, and Iex is a non-oscillatory current due to the extrusion of Ca2+ from the Ca2+-overloaded cytoplasm. Ios and Iex can be present singly or simultaneously. An increase in [Ca2+]i appears to be involved in the short- and long-term compensatory mechanisms that tend to maintain cardiac output in physiological and pathological conditions. Eventually, [Ca2+]i may increase to overload levels and contribute to cardiac failure. Experimental evidence suggests that clinical concentrations of digitalis increase force in Ca2+-overloaded cardiac cells by decreasing the inhibition of the Na+-K+ pump by Ca2+, thereby leading to a reduction in Ca2+ overload and to an increase in force of contraction. 相似文献