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1.
Isolated and cultured neonatal cardiac myocytes contract spontaneously and cyclically. The intracellular concentration of free Ca2+ also changes rhythmically in association with the rhythmic contraction of myocytes (Ca2+ oscillation). Both the contraction and Ca2+ oscillatory rhythms are synchronized among myocytes, and intercellular communication via gap junctions has been considered primarily responsible for the synchronization. However, a recent study has demonstrated that intercellular communication via extracellular ATP‐purinoceptor signaling is also involved in the intercellular synchronization of intracellular Ca2+ oscillation. In this study, we aim to elucidate whether the concentration of extracellular ATP changes cyclically and contributes to the intercellular synchronization of Ca2+ oscillation among myocytes. In almost all the cultured cardiac myocytes at four days in vitro (4 DIV), intracellular Ca2+ oscillations were synchronized with each other. The simultaneous measurement of the concentration of extracellular ATP and intracellular Ca2+ revealed the extracellular concentration of ATP actually oscillated concurrently with the intracellular Ca2+ oscillation. In addition, power spectrum and cross‐correlation analyses suggested that the treatment of cultured cardiac myocytes with suramin, a blocker of P2 purinoceptors, resulted in the asynchronization of Ca2+ oscillatory rhythms among cardiac myocytes. Treatment with suramin also resulted in a significant decrease in the amplitudes of the cyclic changes in both intracellular Ca2+ and extracellular ATP. Taken together, the present study demonstrated the possibility that the concentration of extracellular ATP changes cyclically in association with intracellular Ca2+, contributing to the intercellular synchronization of Ca2+ oscillation among cultured cardiac myocytes.  相似文献   

2.
Isolated and cultured neonatal cardiac myocytes contract spontaneously and cyclically. The contraction rhythms of two isolated cardiac myocytes, each of which beats at different frequencies at first, become synchronized after the establishment of mutual contacts, suggesting that mutual entrainment occurs due to electrical and/or mechanical interactions between two myocytes. The intracellular concentration of free Ca(2+) also changes rhythmically in association with the rhythmic contraction of myocytes (Ca(2+) oscillation), and such a Ca(2+) oscillation was also synchronized among cultured cardiac myocytes. In this study, we investigated whether intercellular communication other than via gap junctions was involved in the intercellular synchronization of intracellular Ca(2+) oscillation in spontaneously beating cultured cardiac myocytes. Treatment with either blockers of gap junction channels or an un-coupler of E-C coupling did not affect the intercellular synchronization of Ca(2+) oscillation. In contrast, treatment with a blocker of P2 purinoceptors resulted in the asynchronization of Ca(2+) oscillatory rhythms among cardiac myocytes. The present study suggested that the extracellular ATP-purinoceptor system was responsible for the intercellular synchronization of Ca(2+) oscillation among cardiac myocytes.  相似文献   

3.
Cultured cardiac myocytes from neonatal rats show spontaneous and rhythmic contractions. The intracellular concentration of free Ca2 +  also changes rhythmically, associated with the rhythmic contraction of myocytes (Ca2 +  oscillation). This study aims to elucidate whether spontaneous rhythmic contraction affects the dynamics of intracellular Ca2 +  oscillation in cultured cardiac myocytes. In cultures at four days in vitro (4 DIV), spontaneous Ca2 +  oscillation was synchronized among myocytes. Treatment of cultures with an uncoupler of E - C coupling resulted in a cessation of the spontaneous contraction of cardiac myocytes, but did not abolish the Ca2 +  oscillation. The intercellular synchronization of intracellular Ca2 +  oscillation persisted, and both the intervals and the fluctuation of the oscillation tended to increase after the termination of rhythmic contraction. The present study demonstrated that mechanical factors associated with rhythmic contraction did not affect the intercellular synchronization of intracellular Ca2 +  oscillation, but possibly contributed to the stability of the oscillatory rhythm.  相似文献   

4.
Isolated and cultured neonatal cardiac myocytes show self-sustaining cyclic contraction, and have the properties of a nonlinear oscillator. We study the dynamics of mechanical contraction and cellular free Ca2+ in a single myocyte for the purposes of gaining an insight into the way in which excitation and contraction processes are inter-related. The concentration of intracellular Ca2+ in the myocyte is also found to vary periodically associated with its rhythmic contraction. The Ca2+ dynamics maintains its self-oscillatory nature when the spontaneous contraction is abolished by pharmacological treatment using 2,3-butanedione monoxime. However, fluctuation analysis of the Ca2+ oscillation intervals reveals that there occurs a characteristic change in the fluctuation behaviour due to the suppression of contraction; the mean value and fluctuation magnitude of the oscillation intervals and the persistency of the fluctuation correlations at short timescales all increase after pharmacological treatment. We develop a new nonlinear model based on Bonhoeffer - van der Pol oscillators to elucidate the mechanisms behind the observed effects of cardiac contraction on the Ca2+ oscillation. The model is composed of three coupled nonlinear differential equations that can describe the dynamics of both excitation (cellular free Ca2+) and contraction. Almost all the experimental findings are successfully reproduced by adjusting a parameter in the model responsible for excitation - contraction coupling.  相似文献   

5.
We analyzed by Fotonic Sensor, a fiber-optic displacement measurement instrument, the effects of heptanol on synchronized contraction of primary neonatal rat cardiac myocytes cultured at confluent density. We also examined the effect of heptanol on the changes in gap junctional intercellular communication by using the microinjection dye transfer method, and on intercellular Ca2+ fluctuation by confocal laser scanning microscopy of myocytes loaded with the fluorescent Ca2+ indicator fluo 3. In addition, we studied expression, phosphorylation, and localization of the major cardiac gap junction protein connexin 43 (Cx43) using immunofluorescence and Western blotting. At Day 6 of culture, numerous myocytes exhibited spontaneous, synchronous contractions, excellent dye coupling, and synchronized intracellular Ca2+ fluctuations. We treated the cells with 1.5, 2.0, 2.5, and 3.0 mmol/liter heptanol. With 1.5 mmol/liter heptanol, we could not observe significant effects on spontaneous contraction of myocytes. At 3.0 mmol/liter, the highest concentration used in the current experiment, heptanol inhibited synchronous contractions and even after washing out of heptanol, synchronous contraction was not rapidly recovered. On the other hand, at the intermediate concentrations of 2.0 and 2.5 mmol/liter, heptanol reversely inhibited synchronized contraction, gap junctional intercellular communication, and synchronization of intracellular Ca2+ fluctuations in the myocytes without preventing contraction and changes of intracellular Ca2+ in individual cells. Brief exposure (5-20 min) to heptanol (2.0 mmol/liter) did not cause detectable changes in the expression, phosphorylation, or localization of Cx43, despite strong inhibition of gap junctional intercellular communication. These results suggest that gap junctional intercellular communication plays an important role in synchronous intracellular Ca2+ fluctuations, which facilitate synchronized contraction of cardiac myocytes.  相似文献   

6.
Airway myocytes are the primary effectors of airway reactivity which modulates airway resistance and hence ventilation. Stimulation of airway myocytes results in an increase in the cytosolic Ca2+ concentration ([Ca2+]i) and the subsequent activation of the contractile apparatus. Many contractile agonists, including acetylcholine, induce [Ca2+]i increase via Ca2+ release from the sarcoplasmic reticulum through InsP3 receptors. Several models have been developed to explain the characteristics of InsP3-induced [Ca2+]i responses, in particular Ca2+ oscillations. The article reviews the modelling of the major structures implicated in intracellular Ca2+ handling, i.e., InsP3 receptors, SERCAs, mitochondria and Ca2+-binding cytosolic proteins. We developed theoretical models specifically dedicated to the airway myocyte which include the major mechanisms responsible for intracellular Ca2+ handling identified in these cells. These biocomputations pointed out the importance of the relative proportion of InsP3 receptor isoforms and the respective role of the different mechanisms responsible for cytosolic Ca2+ clearance in the pattern of [Ca2+]i variations. We have developed a theoretical model of membrane conductances that predicts the variations in membrane potential and extracellular Ca2+ influx. Stimulation of this model by simulated increase in [Ca2+]i predicts membrane depolarisation, but not great enough to trigger a significant opening of voltage-dependant Ca2+ channels. This may explain why airway contraction induced by cholinergic stimulation does not greatly depend on extracellular calcium. The development of such models of airway myocytes is important for the understanding of the cellular mechanisms of airway reactivity and their possible modulation by pharmacological agents.  相似文献   

7.
We investigated the effect of lysophosphatidic acid (LPA), a bioactive phospholipid, on the response in cytosolic free Ca2+ concentration ([Ca2+]i) to mechanical stress in cultured bovine lens epithelial cells. Spritzing of bath solution onto cells as mechanical stress caused marked increase in [Ca2+]i in the presence of LPA and this increase was concentration-dependent (1–10 μM), whereas neither addition of LPA alone nor the mechanical stress in the absence of LPA affected [Ca2+]i. The mechanical stress-induced increase in [Ca2+]i in the presence of LPA was inhibited by removing extracellular Ca2+ or by addition of Gd3+, a blocker of mechanosensitive cation channels, but not by nicardipine, thapsigargin, an inhibitor of endoplasmic reticulum-ATPase pump, or U73122, a phospholipase C inhibitor. These results show that LPA sensitises Ca2+ influx through cation-selective mechanosensitive channels, but does not sensitise Ca2+ release from intracellular stores, triggered by changes in mechanical stress. On the other hand, phosphatidic acid had less of a sensitising effect than LPA, and neither lysophosphatidylcholine nor chlorpromazine had any effect. Also Ca2+ mobilising agonists, ATP, histamine and carbachol, did not sensitise Ca2+ response to the mechanical stress. These results show that LPA sensitises mechanoreceptor-linked response in lens epithelial cells, suggesting that it plays a role in the development of cataracts due to increases in [Ca2+]i induced by mechanical stress.  相似文献   

8.
Magnesium ions (Mg2+) play a fundamental role in cellular function, but the cellular dynamic changes of intracellular Mg2+ remain poorly delineated. The present study aims to clarify whether the concentration of intracellular Mg2+ possibly changes cyclically in association with rhythmic contraction and intracellular Ca2+ oscillation in cultured cardiac myocytes from neonatal rats. To do this, we performed a noise analysis of fluctuations in the concentration of intracellular Mg2+ in cardiac myocytes. The concentration was estimated by loading cells with either Mg‐fluo4/AM or KMG‐20/AM. Results revealed that the intensity of Mg‐fluo‐4 or KMG‐20 fluorescence fluctuated cyclically in association with the rhythmic contraction of cardiac myocytes. In addition, the simultaneous measurement of Fura2 and Mg‐fluo‐4 fluorescence revealed phase differences between the dynamics of the two signals, suggesting that the cyclic changes in the Mg‐fluo‐4 or KMG‐20 fluorescent intensity actually reflected the changes in intracellular Mg2+. The complete termination of spontaneous rhythmic contractions did not abolish Mg2+ oscillations, suggesting that the rhythmic fluctuations in intracellular Mg2+ did not result from mechanical movements. We suggest that the concentration of intracellular Mg2+ changes cyclically in association with spontaneous, cyclic changes in the concentration of intracellular Ca2+ of cardiac myocytes. A noise analysis of the fluctuation of subtle changes in fluorescence intensity could contribute to the elucidation of novel functional roles of Mg2+ in cells.  相似文献   

9.
H Schmidt  G Oettling  U Drews 《FEBS letters》1988,230(1-2):35-37
Activation of muscarinic receptors of heart cells elevates the intracellular Ca2+ concentration. The increase is considered to be due to influx of extracellular Ca2+. We show that intracellular Ca2+ mobilization is involved. Cell suspensions prepared from hearts of 6-day-old chick embryos were loaded with the fluorescent Ca2+ chelator chlortetracycline. Muscarinic stimulation induces a dose-dependent fluorescence decrease (ED50=2.6 × 10−6 M) indicating intracellular Ca2+ mobilization.  相似文献   

10.
Ca2+ mobilization elicited by simulation with brief pulses of high K + were monitored with confocal laser scanned microscopy in intact, guinea pig cardiac myocytes loaded with the calcium indicator fluo-3. Single wavelength ratioing of fluorescence images obtained after prolonged integration times revealed non-uniformities of intracellular Ca2+ changes across the cell, suggesting the presence of significant spatial Ca2+ gradients. Treatment with 20 μM ryanodine, an inhibitor of Ca2+ release from the SR, and 10 μM verapamil, a calcium channel blocker, reduced by 42% and 76% respectively the changes in [Ca2+]i elicited by membrane depolarization. The overall spatial distribution of [Ca2+]i changes appeared unchanged. Ca2+ transients recorded in the presence of verapamil and ryanodine (about 20% of the size of control responses), diminished in the presence of 50 μM 2-4 Dichlorbenzamil (DCB) or 5 mM nickel, two relatively specific inhibitors of the exchange mechanism. Conversely, when the reversal potential of the exchange was shifted to negative potentials by lowering [Na+]0 or by increasing [Na+]i by treatment with 20 μM monensin, the amplitude of these Ca2+ transients increased. Ca2+ transients elicited by membrane depolarization and largely mediated by reverse operation of Na+-Ca2+ exchange could be recorded in the presence of ryanodine, verapamil and monensin. These findings suggest that in intact guinea pig cardiac cells, Ca2+ influx through the exchange mechanism activated by a membrane depolarization in the physiological range can be sufficient to play a significant role in excitation-contraction coupling.  相似文献   

11.
A wasp venom, mastoparan, rapidly increased the cytosolic free Ca2+ concentration ([Ca2+]i) and activated phosphorylase in rat hepatocytes in a concentration-dependent manner. Mastoparan could increase [Ca2+]i even in the absence of extracellular Ca2+, but a larger increase was observed in the presence of extracellular Ca2+. Thus, mastoparan mobilized Ca2+ from intracellular and extracellular Ca2+ stores. It also activated inositol triphosphate (IP3) accumulation, but did not stimulate cAMP production. From these results, we conclude that mastoparan activates rat hepatic glycogenolysis mediated by the accumulation of IP3, which causes an increase of [Ca2+]i but not that mediated by cAMP.  相似文献   

12.
 Isolated and cultured neonatal cardiac myocytes contract spontaneously and cyclically, and have the properties of a non-linear oscillator. In this study, we have analyzed the relationship between the fluctuation of contraction rhythm of spontaneously beating cultured cardiac myocytes, and the coupling strength among them. The coefficient of variation of contraction intervals increased transiently in the early stages of incubation, and then decreased almost monotonically with time. The contraction rhythm of the myocytes became synchronized in the late stage of the culture. The day on which synchronization occurred almost coincided with the day when the coefficient of variation reached its lowest value. In addition, we have performed a mathematical analysis using interacting Bonhoeffer–van der Pol oscillators to clarify the mechanisms underlying the changes in the fluctuation of contraction rhythm with time. As the coupling strength among oscillators increased, the coefficient of variation of oscillation periods increased temporarily, but then decreased rapidly when the oscillators showed synchronization. These results suggest that the changes in the fluctuation of beating rhythm result from the increase in strength of electrical coupling among spontaneously beating cardiac myocytes. Received: 10 August 2000 / Accepted in revised form: 19 August 2001  相似文献   

13.
In cultured pituatary gonadotrophs, gonadotropin-releasing hormone (GnRH) caused dose-dependent and biphasic increases in cytoplasmic calcium concentration ([Ca2+]i) and LH release. Both extra- and intracellular calcium pools participate in GnRH-induced elevation of [Ca2+]i and LH secretion. The spike phase of the [Ca2+]i response represents the primary signal derived predominantly from the rapid mobilization of intracellular Ca2+. In contrast, the prolonged phase of the Ca2+ signal depends exclusively on Ca2+ entry from the extracellular pool. The influx of Ca2+ occurs partially through dihydropyridine-sensitive calcium channels. Both [Ca2+]i and LH responses to increasing concentrations of GnRH occur over very similar time scales, suggesting that increasing degrees of receptor occupancy are transduced into amplitude-modulated Ca2+ responses, which in turn activate exocytosis in a linear manner. However, several lines of evidence indicated the complexity over the relationship between Ca2+ signaling and LH exocytosis. In contrast to [Ca2+]i measurements in cell suspension, single cell Ca2+ measurements revealed the existence of a more complicated pattern of Ca2+ response to GnRH, with a biphasic response to high agonist doses and prominent oscillatory responses to lower GnRH concentrations, with a log-linear correlation between GnRH dose and the frequency of Ca2+ spiking. In addition, analysis of the magnitudes of the magnitudes of the [Ca2+]i and LH responses of gonadotrophs to a wide range of GnRH concentrations in the presence and absence of extracellular Ca2+, and to K+ and phorbol ester stimulation, showed non-linearity between these parameters with amplification of [Ca2+]i-mediated exocytosis. Studies on cell depleted of protein kinase C under conditions that did not change the LH pool suggested the participation of protein kinase C in this amplication, especially during the plateau phase of the secretory response to GnRH.  相似文献   

14.
To quantitatively understand intracellular Na+ and Cl homeostasis as well as roles of Na+/K+ pump and cystic fibrosis transmembrane conductance regulator Cl channel (ICFTR) during the β1-adrenergic stimulation in cardiac myocyte, we constructed a computer model of β1-adrenergic signaling and implemented it into an excitation-contraction coupling model of the guinea-pig ventricular cell, which can reproduce membrane excitation, intracellular ion changes (Na+, K+, Ca2+ and Cl), contraction, cell volume, and oxidative phosphorylation. An application of isoproterenol to the model cell resulted in the shortening of action potential duration (APD) after a transient prolongation, the increases in both Ca2+ transient and cell shortening, and the decreases in both Cl concentration and cell volume. These results are consistent with experimental data. Increasing the density of ICFTR shortened APD and augmented the peak amplitudes of the L-type Ca2+ current (ICaL) and the Ca2+ transient during the β1-adrenergic stimulation. This indirect inotropic effect was elucidated by the increase in the driving force of ICaL via a decrease in plateau potential. Our model reproduced the experimental data demonstrating the decrease in intracellular Na+ during the β-adrenergic stimulation at 0 or 0.5 Hz electrical stimulation. The decrease is attributable to the increase in Na+ affinity of Na+/K+ pump by protein kinase A. However it was predicted that Na+ increases at higher beating rate because of larger Na+ influx through forward Na+/Ca2+ exchange. It was demonstrated that dynamic changes in Na+ and Cl fluxes remarkably affect the inotropic action of isoproterenol in the ventricular myocytes.  相似文献   

15.
Glucose-induced insuline release, glucose-induced rises in intracellular free Ca2+ concentration ([Ca2+]i), and voltage-dependent Ca2+ channel activity were assessed in monolayer cultures of β-vells 3–5 day-old rats. The glucose-stimulated insulin secretory responses and [Ca2+]i rises were like those in adult rat β-cells rather than fetal rat β-cells. Voltage-dependent Ca2+ channel antagonists decreased glucose-induced insulin secretion, aborted the [Ca2+]2 rise and, like deprivation of extracellular Ca2+, prevented the glucose-induced rise in [Ca2+]i when added before the glucose challenge. The presence of nifedipine-sensitive, voltage-dependent Ca2+ channels was demonstrated directly by measuring Ca2+ currents using the whole-cell configuration of the patch-clamp technique and indirectly by measuring [Ca2+]1 after membrane depolarization by 45 mMm K+ or 200 μM tolbutamide. Thus, in cultured β-cells of 3–5 day-old rats the coupling of glucose stimulation to Ca2+ influx is essentially mature, in contrast to what has been reported for fetal or very early neonatal cells.  相似文献   

16.
The effects of K+ channel modulators, tetraethylammonium, 4-aminopyridine and diazoxide, and high extracellular K+ on cell growth and agonist-induced intracellular Ca2+ mobilization were investigated. Two human brain tumour cell lines, U-373 MG astrocytoma and SK-N-MC neuroblastoma, were used as model cellular systems. K+ channel modulators and increased extracellular K+ concentration inhibited tumour cell growth in a dose-related fashion in both cell lines. In addition, agonist (carbachol or serum)-induced intracellular Ca2+ mobilization was also blocked by the pretreatment of growth-inhibitory concentrations of K+ channel modulators and high extracellular K+. Thus, these results suggest that K+ channel modulators are effective inhibitors of brain tumour cell growth and that their growth regulation may be due to the interference with the intracellular Ca2+ signalling mechanisms.  相似文献   

17.
Oxidative stress appears to be implicated in the pathogenesis of various diseases including hepatotoxicity. Although intracellular Ca2+ signals have been suggested to play a role in the oxidative damage of hepatocytes, the sources and effects of oxidant-induced intracellular Ca2+ increases are currently debatable. Thus, in this study we investigated the exact source and mechanism of oxidant-induced liver cell damage using HepG2 human hepatoma cells as a model liver cellular system. Treatment with 200 μM of tert-butyl hydroperoxide (tBOOH) induced a sustained increase in the level of intracellular reactive oxygen intermediates (ROI) and apoptosis, assessed by 2',7'-dichlorofluorescein fluorescence and flow cytometry, respectively. Antioxidants, N-acetyl cysteine (NAC) or N,N'-diphenyl-p-phenylenediamine significantly inhibited both the ROI generation and apoptosis. In addition, tBOOH induced a slow and sustained increase in intracellular Ca2+ concentration, which was completely prevented by the antioxidants. An intracellular Ca2+ chelator, bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid/cetoxymethyl ester significantly suppressed the tBOOH-induced apoptosis. These results imply that activation of an intracellular Ca2+ signal triggered by increased ROI may mediate the tBOOH-induced apoptosis. Both intracellular Ca2+ increase and induction of apoptosis were significantly inhibited by an extracellular Ca2+ chelator or Na+/Ca2+ exchanger blockers (bepridil and benzamil), whereas neither Ca2+ channel antagonists (verapamil and nifedipine) nor a nonselective cation channel blocker (flufenamic acid) had an effect. These results suggest that tBOOH may increase intracellular Ca2+ through the activation of reverse mode of Na+/Ca2+ exchanger. However, tBOOH decreased intracellular Na+ concentration, which was completely prevented by NAC. These results indicate that ROI generated by tBOOH may increase intracellular Ca2+ concentration by direct activation of the reverse mode of Na+/Ca>2+ exchanger, rather than indirect elevation of intracellular Na+ levels. Taken together, these results suggest that the oxidant, tBOOH induced apoptosis in human HepG2 cells and that intracellular Ca2+ may mediate this action of tBOOH. These results further suggest that Na+/Ca2+ exchanger may be a target for the management of oxidative hepatotoxicity.  相似文献   

18.
Increase in cytoplasmic cyclic AMP concentration stimulates Ca2+ influx through the cyclic AMP-gated cation channel in the plasma membrane of cultured carrot cells. However, the Ca2+ current terminated after a few minutes even in the presence of high concentrations of cyclic AMP indicating that hydrolysis of the nucleotide is not responsible for stop of the Ca2+ influx. Cyclic AMP evoked discharge of Ca2+ from inside-out sealed vesicles of carrot plasma membrane, and it was strongly inhibited when the suspension of the vesicles was supplemented with 1 μM of free Ca2+, while Ca2+ lower than 0.1 μM did not affect the Ca2+-release. The Ca2+ flux across plasma membrane was restored from this Ca2+-induced inhibition by the addition of calmodulin inhibitors or anti-calmodulin. These results suggest that Ca2+ influx initiated by the increase in intracellular cAMP in cultured carrot cells is terminated when the cytosolic Ca2+ concentration reaches the excitatory level in the cells, and calmodulin located in the plasma membrane plays an important role in the response decay of the cyclic nucleotide-gated Ca2+ channel.  相似文献   

19.
The inactivation of the L-type Ca2+ current is composed of voltage-dependent and calcium-dependent mechanisms. The relative contribution of these processes is still under dispute and the idea that the voltage-dependent inactivation could be subject to further modulation by other physiological processes had been ignored. This study sought to model physiological modulation of inactivation of the current in cardiac ventricular myocytes, based upon the recent detailed experimental data that separated total and voltage-dependent inactivation (VDI) by replacing extracellular Ca2+ with Mg2+ and monitoring L-type Ca2+ channel behaviour by outward K+ current flowing through the channel in the absence of inward current flow. Calcium-dependent inactivation (CDI) was based upon Ca2+ influx and formulated from data that was recorded during β-adrenergic stimulation of the myocytes. Ca2+ influx and its competition with non-selective monovalent cation permeation were also incorporated into channel permeation in the model. The constructed model could closely reproduce the experimental Ba2+ and Ca2+ current results under basal condition where no β-stimulation was added after a slight reduction of the development of fast voltage-dependent inactivation with depolarization. The model also predicted that under β-adrenergic stimulation voltage-dependent inactivation is lost and calcium-dependent inactivation largely compensates it. The developed model thus will be useful to estimate the respective roles of VDI and CDI of L-type Ca2+ channels in various physiological and pathological conditions of the heart which would otherwise be difficult to show experimentally.  相似文献   

20.
We invetigate the mechanisms underlying the intracellular calcium pulse that occurs in response to extracellular adenosine triphosphate (ATP) in osteoclasts. We find that pre-loading of GDP-β-S abolishes the response in Ca2+-free medium, demonstrating an internal release of Ca2+ via a pathway that involves a G protein. GDP-β-S does not block in normal Ca2+-containing medium, suggesting that ATP also induces a Ca2+ influx across the cell membrane. We confirmed this using the Mn2+ quenching technique, which shows significant opening of Ca2+ channels. We find a smaller response to adenosine diphosphate (ADP) and 2-methylthio-ATP (2-MeSATP), but no response to β, γ-methylene-ATP (AMP-PCP), adenosine monophosphate (AMP) or uridine triphosphate (UTP). Prior application of AMP and UTP, but not AMP-PCP, blocks the response to ATP. Our resutls indicate that the receptor is a P2 subtype that is not characteristic of any previously reported P2 receptor or combination of P2 receptors.  相似文献   

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