共查询到20条相似文献,搜索用时 31 毫秒
1.
McCullough Laura A.; Egan Terrance M.; Westfall Thomas C. 《American journal of physiology. Cell physiology》1998,274(5):C1290
We previouslydemonstrated, using rat PC-12 pheochromocytoma cells differentiated toa sympathetic neuronal phenotype with nerve growth factor (NGF), thatneuropeptide Y (NPY) inhibits catecholamine synthesis as well asrelease. Inquiry into the mechanisms of these inhibitions implicateddistinct pathways involving reduction ofCa2+ influx throughvoltage-activated Ca2+ channels.In the present investigation the effects of NPY on whole cellBa2+ currents were examined toobtain direct evidence supporting the mechanisms suggested by thosestudies. NPY was found to inhibit the voltage-activatedBa2+ current in NGF-differentiatedPC-12 cells in a reversible fashion with anEC50 of 13 nM. This inhibition waspertussis toxin sensitive and resulted from NPY modulation of L- andN-type Ca2+ channels. Theinhibition of L-type channels was not seen with <1 nM freeintracellular Ca2+ or when proteinkinase C (PKC) was inhibited by chelerythrine or PKC-(1931).Furthermore, the effect of NPY on L-type channels was mimicked by thePKC activator phorbol 12-myristate 13-acetate. These studiesdemonstrate that, in addition to inhibition of N-type Ca2+ channels, inNGF-differentiated PC-12 cells NPY inhibits L-type Ca2+ channels via an intracellularCa2+- and PKC-dependent pathway. 相似文献
2.
Kockskämper J Ahmmed GU Zima AV Sheehan KA Glitsch HG Blatter LA 《American journal of physiology. Cell physiology》2004,287(2):C527-C538
Palytoxin is a coral toxin that seriously impairs heart function, but its effects on excitation-contraction (E-C) coupling have remained elusive. Therefore, we studied the effects of palytoxin on mechanisms involved in atrial E-C coupling. In field-stimulated cat atrial myocytes, palytoxin caused elevation of diastolic intracellular Ca2+ concentration ([Ca2+]i), a decrease in [Ca2+]i transient amplitude, Ca2+ alternans followed by [Ca2+]i waves, and failures of Ca2+ release. The decrease in [Ca2+]i transient amplitude occurred despite high sarcoplasmic reticulum (SR) Ca2+ load. In voltage-clamped myocytes, palytoxin induced a current with a linear current-voltage relationship (reversal potential 5 mV) that was blocked by ouabain. Whole cell Ca2+ current and ryanodine receptor Ca2+ release channel function remained unaffected by the toxin. However, palytoxin significantly reduced Ca2+ pumping of isolated SR vesicles. In current-clamped myocytes stimulated at 1 Hz, palytoxin induced a depolarization of the resting membrane potential that was accompanied by delayed afterdepolarizations. No major changes of action potential configuration were observed. The results demonstrate that palytoxin interferes with the function of the sarcolemmal Na+-K+ pump and the SR Ca2+ pump. The suggested mode of palytoxin toxicity in the atrium involves the conversion of Na+-K+ pumps into nonselective cation channels as a primary event followed by depolarization, Na+ accumulation, and Ca2+ overload, which, in turn, causes arrhythmogenic [Ca2+]i waves and delayed afterdepolarizations. atrial myocytes; intracellular calcium 相似文献
3.
Ding Y Schwartz D Posner P Zhong J 《American journal of physiology. Cell physiology》2004,287(2):C413-C421
It has been suggested that L-type Ca2+ channels play an important role in cell swelling-induced vasoconstriction. However, there is no direct evidence that Ca2+ channels in vascular smooth muscle are modulated by cell swelling. We tested the hypothesis that L-type Ca2+ channels in rabbit portal vein myocytes are modulated by hypotonic cell swelling via protein kinase activation. Ba2+ currents (IBa) through L-type Ca2+ channels were recorded in smooth muscle cells freshly isolated from rabbit portal vein with the conventional whole cell patch-clamp technique. Superfusion of cells with hypotonic solution reversibly enhanced Ca2+ channel activity but did not alter the voltage-dependent characteristics of Ca2+ channels. Bath application of selective inhibitors of protein kinase C (PKC), Ro-318425 or Go-6983, prevented IBa enhancement by hypotonic swelling, whereas the specific protein kinase A (PKA) inhibitor KT-5720 had no effect. Bath application of phorbol 12,13-dibutyrate (PDBu) significantly increased IBa under isotonic conditions and prevented current stimulation by hypotonic swelling. However, PDBu did not have any effect on IBa when cells were first exposed to hypotonic solution. Furthermore, downregulation of endogenous PKC by overnight treatment of cells with PDBu prevented current enhancement by hypotonic swelling. These data suggest that hypotonic cell swelling can enhance Ca2+ channel activity in rabbit portal vein smooth muscle cells through activation of PKC. cell swelling; protein kinases; calcium current 相似文献
4.
HU ZhiTao DUN XinPeng ZHANG Ming ZHU HongLiang XIE Li WU ZhengXing CHEN ZhengWang XU Tao
《中国科学:生命科学英文版》2007,50(3):285-291
《中国科学:生命科学英文版》2007,50(3):285-291
Using alginic acid to adsorb polypeptides at pH 2.7, we isolated a peptide pea albumin 1b (PA1b) from pea seeds. The PA1b is a single chain peptide consisting of 37 amino acid residues with 6 cysteines which constitutes the cystine-knot structure. Using microfluorometry and patch clamp techniques, we found that PA1b significantly elevated the intracellular calcium level ([Ca2 ]i) and elicited membrane capacitance increase in the primary rat pancreatic β cells. The PA1b effect on [Ca2 ]i elevation was abolished in the absence of extracellular Ca2 or in the presence of L-type Ca2 channel blocker, nimodipine. Interestingly, we found that PA1b significantly depolarized membrane potential, which could lead to the opening of voltage-dependent L-type Ca2 channels and influx of extracellular Ca2 , and then evoke robust secretion. In this study we identified the plant peptide PA1b which is capable of affecting the excitability and function of mammalian pancreatic β cell. 相似文献
5.
Yu X Chen XW Zhou P Yao L Liu T Zhang B Li Y Zheng H Zheng LH Zhang CX Bruce I Ge JB Wang SQ Hu ZA Yu HG Zhou Z 《American journal of physiology. Cell physiology》2007,292(3):C1147-C1155
The hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, or cardiac (If)/neuronal (Ih) time- and voltage-dependent inward cation current channels, are conventionally considered as monovalent-selective channels. Recently we discovered that calcium ions can permeate through HCN4 and Ih channels in neurons. This raises the possibility of Ca2+ permeation in If, the Ih counterpart in cardiac myocytes, because of their structural homology. We performed simultaneous measurement of fura-2 Ca2+ signals and whole cell currents produced by HCN2 and HCN4 channels (the 2 cardiac isoforms present in ventricles) expressed in HEK293 cells and by If in rat ventricular myocytes. We observed Ca2+ influx when HCN/If channels were activated. Ca2+ influx was increased with stronger hyperpolarization or longer pulse duration. Cesium, an If channel blocker, inhibited If and Ca2+ influx at the same time. Quantitative analysis revealed that Ca2+ flux contributed to 0.5% of current produced by the HCN2 channel or If. The associated increase in Ca2+ influx was also observed in spontaneously hypertensive rat (SHR) myocytes in which If current density is higher than that of normotensive rat ventricle. In the absence of EGTA (a Ca2+ chelator), preactivation of If channels significantly reduced the action potential duration, and the effect was blocked by another selective If channel blocker, ZD-7288. In the presence of EGTA, however, preactivation of If channels had no effects on action potential duration. Our data extend our previous discovery of Ca2+ influx in Ih channels in neurons to If channels in cardiac myocytes. calcium ion flux; hyperpolarization-activated, cyclic nucleotide-gated/cardiac time- and volume-dependent cation current channels 相似文献
6.
Ingalls Christopher P.; Warren Gordon L.; Williams Jay H.; Ward Christopher W.; Armstrong R. B. 《Journal of applied physiology》1998,85(1):58-67
The objectives of this research were to determine thecontribution of excitation-contraction (E-C) coupling failure to the decrement in maximal isometric tetanic force(Po) in mouse extensor digitorumlongus (EDL) muscles after eccentric contractions and to elucidatepossible mechanisms. The left anterior crural muscles of femaleICR mice (n = 164) wereinjured in vivo with 150 eccentric contractions.Po, caffeine-,4-chloro-m-cresol-, andK+-induced contracture forces,sarcoplasmic reticulum (SR) Ca2+release and uptake rates, and intracellularCa2+ concentration([Ca2+]i)were then measured in vitro in injured and contralateral control EDLmuscles at various times after injury up to 14 days. On the basis ofthe disproportional reduction inPo (~51%) compared with caffeine-induced force (~11-21%), we estimate that E-C coupling failure can explain 57-75% of thePo decrement from 0 to 5 days postinjury. Comparable reductions inPo andK+-induced force (51%), and minorreductions (0-6%) in the maximal SRCa2+ release rate, suggest thatthe E-C coupling defect site is located at the t tubule-SR interfaceimmediately after injury. Confocal laser scanning microscopy indicatedthat resting[Ca2+]iwas elevated and peak tetanic[Ca2+]iwas reduced, whereas peak4-chloro-m-cresol-induced[Ca2+]iwas unchanged immediately after injury. By 3 days postinjury, 4-chloro-m-cresol-induced[Ca2+]ibecame depressed, probably because of decreased SRCa2+ release and uptake rates(17-31%). These data indicate that the decrease inPo during the first several daysafter injury primarily stems from a failure in the E-C couplingprocess. 相似文献
7.
Micromolar Ca2+ from sparks activates Ca2+-sensitive K+ channels in rat cerebral artery smooth muscle 总被引:3,自引:0,他引:3
Perez Guillermo J.; Bonev Adrian D.; Nelson Mark T. 《American journal of physiology. Cell physiology》2001,281(6):C1769
The goal of the present study was to testthe hypothesis that local Ca2+ release events(Ca2+ sparks) deliver high local Ca2+concentration to activate nearby Ca2+-sensitiveK+ (BK) channels in the cell membrane of arterial smoothmuscle cells. Ca2+ sparks and BK channels were examined inisolated myocytes from rat cerebral arteries with laser scanningconfocal microscopy and patch-clamp techniques. BK channels had anapparent dissociation constant for Ca2+ of 19 µM and aHill coefficient of 2.9 at 40 mV. At near-physiological intracellularCa2+ concentration ([Ca2+]i; 100 nM) and membrane potential (40 mV), the open probability of a singleBK channel was low (1.2 × 106). A Ca2+spark increased BK channel activity to 18. Assuming that 1-100% of the BK channels are activated by a single Ca2+ spark, BKchannel activity increases 6 × 105-fold to 6 × 103-fold, which corresponds to ~30 µM to 4 µM sparkCa2+ concentration.1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acidacetoxymethyl ester caused the disappearance of all Ca2+sparks while leaving the transient BK currents unchanged. Our resultssupport the idea that Ca2+ spark sites are in closeproximity to the BK channels and that local[Ca2+]i reaches micromolar levels to activateBK channels. 相似文献
8.
Effects of osmotic shrinkage on voltage-gated Ca2+ channel currents in rat anterior pituitary cells 总被引:1,自引:0,他引:1
Ben-Tabou De-Leon S Ben-Zeev G Nussinovitch I 《American journal of physiology. Cell physiology》2006,290(1):C222-C232
Increased extracellular osmolarity ([Os]e) suppresses stimulated hormone secretion from anterior pituitary cells. Ca2+ influx may mediate this effect. We show that increase in [Os]e (by 18125%) differentially suppresses L-type and T-type Ca2+ channel currents (IL and IT, respectively); IL was more sensitive than IT. Hyperosmotic suppression of IL depended on the magnitude of increase in [Os]e and was correlated with the percent decrease in pituitary cell volume, suggesting that pituitary cell shrinkage can modulate L-type currents. The hyperosmotic suppression of IL and IT persisted after incubation of pituitary cells either with the actin-disrupter cytochalasin D or with the actin stabilizer phalloidin, suggesting that the actin cytoskeleton is not involved in this modulation. The hyperosmotic suppression of Ca2+ influx was not correlated with changes in reversal potential, membrane capacitance, and access resistance. Together, these results suggest that the hyperosmotic suppression of Ca2+ influx involves Ca2+ channel proteins. We therefore recorded the activity of L-type Ca2+ channels from cell-attached patches while exposing the cell outside the patch pipette to hyperosmotic media. Increased [Os]e reduced the activity of Ca2+ channels but did not change single-channel conductance. This hyperosmotic suppression of Ca2+ currents may therefore contribute to the previously reported hyperosmotic suppression of hormone secretion. L-type Ca2+ channels; osmosensitivity; mechanosensitivity; osmolarity; hyperosmolarity 相似文献
9.
Activation of calcium release assessed by calcium release-induced inactivation of calcium current in rat cardiac myocytes 总被引:4,自引:0,他引:4
Zahradníková A Kubalová Z Pavelková J Györke S Zahradník I 《American journal of physiology. Cell physiology》2004,286(2):C330-C341
In mammalian cardiac myocytes, calcium released into the dyadic space rapidly inactivates calcium current (ICa). We used this Ca2+ release-dependent inactivation (RDI) of ICa as a local probe of sarcoplasmic reticulum Ca2+ release activation. In whole cell patch-clamped rat ventricular myocytes, Ca2+ entry induced by short prepulses from 50 mV to positive voltages caused suppression of peak ICa during a test pulse. The negative correlation between peak ICa suppression and ICa inactivation during the test pulse indicated that RDI evoked by the prepulse affected only calcium channels in those dyads in which calcium release was activated. Ca2+ ions injected during the prepulse and during the subsequent tail current suppressed peak ICa in the test pulse to a different extent. Quantitative analysis indicated that equal Ca2+ charge was 3.5 times less effective in inducing release when entering during the prepulse than when entering during the tail. Tail Ca2+ charge injected by the first voltage-dependent calcium channel (DHPR) openings was three times less effective than that injected by DHPR reopenings. These findings suggest that calcium release activation can be profoundly influenced by the recent history of L-type Ca2+ channel activity due to potentiation of ryanodine receptors (RyRs) by previous calcium influx. This conclusion was confirmed at the level of single RyRs in planar lipid bilayers: using flash photolysis of the calcium cage NP-EGTA to generate two sequential calcium stimuli, we showed that RyR activation in response to the second stimulus was four times higher than that in response to the first stimulus. excitation-contraction coupling 相似文献
10.
Pregnant rat myometrial cells show heterogeneous ryanodine- and caffeine-sensitive calcium stores 总被引:4,自引:0,他引:4
Martin Cecile; Hyvelin Jean-Marc; Chapman Karen E.; Marthan Roger; Ashley Richard H.; Savineau Jean-Pierre 《American journal of physiology. Cell physiology》1999,277(2):C243
IntracellularCa2+ release channels such asryanodine receptors play crucial roles in theCa2+-mediated signaling thattriggers excitation-contraction coupling in muscles. Although theexistence and the role of these channels are well characterized inskeletal and cardiac muscles, their existence in smooth muscles, andmore particularly in the myometrium, is very controversial. We have nowclearly demonstrated the expression of ryanodine receptorCa2+ release channels in ratmyometrial smooth muscle, and for the first time, intracellularCa2+ concentration experimentswith indo 1 on single myometrial cells have revealed the existence of afunctional ryanodine- and caffeine-sensitive Ca2+ release mechanism in 30% ofrat myometrial cells. RT-PCR and RNase protection assay on wholemyometrial smooth muscle demonstrate the existence of all threeryr mRNAs in the myometrium:ryr3 mRNA is the predominant subtype,with much lower levels of expression forryr1 andryr2 mRNAs, suggesting that theryanodine Ca2+ release mechanismin rat myometrium is largely encoded byryr3. Moreover, using intracellularCa2+ concentration measurementsand RNase protection assays, we have demonstrated that the expression,the percentage of cells responding to ryanodine, and the function ofthese channels are not modified during pregnancy. 相似文献
11.
Long-lasting muscle fatigue: partial disruption of excitation-contraction coupling by elevated cytosolic Ca2+ concentration during contractions 总被引:1,自引:0,他引:1
The repeated elevation of cytosolic Ca2+ concentration ([Ca2+]i) above resting levels during contractile activity has been associated with long-lasting muscle fatigue. The mechanism underlying this fatigue appears to involve elevated [Ca2+]i levels that induce disruption of the excitation-contraction (E-C) coupling process at the triad junction. Unclear, however, are which aspects of the activity-related [Ca2+]i changes are responsible for the deleterious effects, in particular whether they depend primarily on the peak [Ca2+]i reached locally at particular sites or on the temporal summation of the increased [Ca2+] in the cytoplasm as a whole. In this study, we used mechanically skinned fibers from rat extensor digitorum longus muscle, in which the normal E-C coupling process remains intact. The [Ca2+]i was raised either by applying a set elevated [Ca2+] throughout the fiber or by using action potential stimulation to induce the release of sarcoplasmic reticulum Ca2+ by the normal E-C coupling system with or without augmentation by caffeine or buffering with BAPTA. Herein we show that elevating [Ca2+]i in the physiological range of 220 µM irreversibly disrupts E-C coupling in a concentration-dependent manner but requires exposure for a relatively long time (13 min) to cause substantial uncoupling. The effectiveness of Ca2+ released via the endogenous system in disrupting E-C coupling indicates that the relatively high [Ca2+]i attained close to the release site at the triad junction is a more important factor than the increase in bulk [Ca2+]i. Our results suggest that during prolonged vigorous activity, the many repeated episodes of relatively high triadic [Ca2+] can disrupt E-C coupling and lead to long-lasting fatigue. skeletal muscle; low-frequency fatigue; ryanodine receptor; skinned fiber 相似文献
12.
ZHANG Guangqin FU Yu Yang Dongmei HAO Xuemei BAI Shuhua TANG Yiqun Edward G LAKATTA WU Caihong CHENG Heping 《中国科学C辑(英文版)》2004,47(1):31-37
Ca2+ sparks are the elementary events of intracellular Ca2+ release from the sarcoplasmic reticulum in cardiac myocytes. In order to investigate whether spontaneous L-type Ca2+ channel activation contributes to the genesis of spontaneous Ca2+ sparks, we used confocal laser scanning microscopy and fluo-4 to visualize local Ca2+ sparks in intact rat ventricular myocytes. In the presence of 0.2 mmol/L CdCI2 which inhibits spontaneous L-type Ca2+ channel activation, the rate of occurrence of spontaneous Ca2+ sparks was halved from 4.20 to 2.04 events/(100 μm · s), with temporal and spatial properties of individual Ca2+ sparks unchanged. Analysis of the Cd2+-sensitive spark production revealed an open probability of ~10
-5
for L-type channels at the rest membrane potentials (-80 mV). Thus, infrequent and stochastic openings of sarcolemmal L-type
Ca2+ channels in resting heart cells contribute significantly to the production of spontaneous Ca2+ sparks. 相似文献
13.
Taylor S. C.; Green K. N.; Smith I. F.; Peers C. 《American journal of physiology. Cell physiology》2001,281(6):C1850
The toxic actions of scrapie prion protein(PrPsc) are poorly understood. We investigated the abilityof the toxic PrPsc fragment 106-126 to interfere withevoked catecholamine secretion from PC-12 cells. Prion protein fragment106-126 (PrP106-126) caused a time- andconcentration-dependent augmentation of exocytosis due to the emergenceof a Ca2+ influx pathway resistant to Cd2+ butsensitive to other inorganic cations. In control cells, secretion wasdependent on Ca2+ influx through L- and N-typeCa2+ channels, but after exposure to PrP106-126,secretion was unaffected by N-type channel blockade. Instead, selectiveL-type channel blockade was as effective as Cd2+ insuppressing secretion. Patch-clamp recordings revealed no change intotal Ca2+ current density in PrP106-126-treated cellsor in the contribution to total current of L-type channels, but a smallCd2+-resistant current was found only inPrP106-126-treated cells. Thus PrP106-126 augments secretionby inducing a Cd2+-resistant Ca2+ influxpathway and alters coupling of native Ca2+ channels toexocytosis. These effects are likely contributory factors in the toxiccellular actions of PrPsc. 相似文献
14.
Palmer Bradley M.; Thayer Anne M.; Snyder Steven M.; Moore Russell L. 《Journal of applied physiology》1998,85(6):2159-2168
The effects of run endurance training and fura 2 loading on the contractile function andCa2+ regulation of rat leftventricular myocytes were examined. In myocytes not loaded with fura 2, the maximal extent of myocyte shortening was reduced with trainingunder our pacing conditions [0.5 Hz at 2.0 and 0.75 mM externalCa2+ concentration([Ca2+]o)], although training had noeffect on the temporal characteristics. The "light" loading ofmyocytes with fura 2 markedly suppressed (~50%) maximal shorteningin the sedentary and trained groups, although the temporalcharacteristics of myocyte shortening were significantly prolonged inthe trained group. No discernible differences in the dynamiccharacteristics of the intracellularCa2+ concentration([Ca2+]) transientwere detected at 2.0 mM[Ca2+]o, althoughpeak [Ca2+] and rateof [Ca2+] rise duringcaffeine contracture were greater in the trained state at 0.75 mM[Ca2+]o. We concludethat training induced a diminished myocyte contractile function underthe conditions studied here and a more effective coupling of inwardCa2+ current to sarcoplasmicreticulum Ca2+ release at low[Ca2+]o,and that fura 2 and its loading vehicle DMSO significantly alter theintrinsic characteristics of myocyte contractile function andCa2+ regulation. 相似文献
15.
Coupling strength between localized Ca(2+) transients and K(+) channels is regulated by protein kinase C 总被引:1,自引:0,他引:1
Bayguinov O Hagen B Kenyon JL Sanders KM 《American journal of physiology. Cell physiology》2001,281(5):C1512-C1523
Localized Ca2+ transients resulting from inositoltrisphosphate (IP3)-dependent Ca2+ releasecouple to spontaneous transient outward currents (STOCs) in murinecolonic myocytes. Confocal microscopy and whole cell patch-clamptechniques were used to investigate coupling between localizedCa2+ transients and STOCs. Colonic myocytes were loadedwith fluo 3. Reduction in external Ca2+([Ca2+]o) reduced localized Ca2+transients but increased STOC amplitude and frequency. Simultaneous recordings of Ca2+ transients and STOCs showed increasedcoupling strength between Ca2+ transients and STOCs when[Ca2+]o was reduced. Gd3+ (10 µM) did not affect Ca2+ transients but increased STOCamplitude and frequency. Similarly, an inhibitor of Ca2+influx,1-2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole (SKF-96365), increased STOC amplitude and frequency. A protein kinase C(PKC) inhibitor, GF-109203X, also increased the amplitude and frequencyof STOCs but had no effect on Ca2+ transients. Phorbol12-myristate 13-acetate (1 µM) reduced STOC amplitude and frequencybut did not affect Ca2+ transients. 4-Phorbol (1 µM)had no effect on STOCs or Ca2+ transients. Single channelstudies indicated that large-conductance Ca2+-activatedK+ (BK) channels were inhibited by aCa2+-dependent PKC. In summary 1)Ca2+ release from IP3 receptor-operated storesactivates Ca2+-activated K+ channels;2) Ca2+ influx through nonselective cationchannels facilitates activation of PKC; and 3) PKC reducesthe Ca2+ sensitivity of BK channels, reducing the couplingstrength between localized Ca2+ transients and BK channels. 相似文献
16.
Yano S Ishikawa T Tsuda H Obara K Nakayama K 《American journal of physiology. Cell physiology》2005,288(3):C702-C709
A hyposmotic challenge elicited contraction of isolated canine basilar arteries. The contractile response was nearly abolished by the removal of extracellular Ca2+ and by the voltage-dependent Ca2+ channel (VDCC) blocker nicardipine, but it was unaffected by thapsigargin, which depletes intracellular Ca2+ stores. The contraction was also inhibited by Gd3+ and ruthenium red, cation channel blockers, and Cl channel blockers DIDS and niflumic acid. The reduction of extracellular Cl concentrations enhanced the hypotonically induced contraction. Patch-clamp analysis showed that a hyposmotic challenge activated outwardly rectifying whole cell currents in isolated canine basilar artery myocytes. The reversal potential of the current was shifted toward negative potentials by reductions in intracellular Cl concentration, indicating that the currents were carried by Cl. Moreover, the currents were abolished by 10 mM BAPTA in the pipette solution and by the removal of extracellular Ca2+. Taken together, these results suggest that a hyposmotic challenge activates cation channels, which presumably cause Ca2+ influx, thereby activating Ca2+-activated Cl channels. The subsequent membrane depolarization is likely to increase Ca2+ influx through VDCC and elicit contraction. stretch-activated cation channels; Ca2+-activated Cl channels; voltage-dependent Ca2+ channels; large-conductance Ca2+-activated K+ channels; gadolinium 相似文献
17.
Regulation of dynamic behavior of cardiac ryanodine receptor by Mg2+ under simulated physiological conditions 总被引:1,自引:0,他引:1
Zahradníková A Dura M Györke I Escobar AL Zahradník I Györke S 《American journal of physiology. Cell physiology》2003,285(5):C1059-C1070
Mg2+, an important constituent of the intracellular milieu in cardiac myocytes, is known to inhibit ryanodine receptor (RyR) Ca2+ release channels by competing with Ca2+ at the cytosolic activation sites of the channel. However, the significance of this competition for local, dynamic Ca2+-signaling processes thought to govern cardiac excitation-contraction (EC) coupling remains largely unknown. In the present study, Ca2+ stimuli of different waveforms (i.e., sustained and brief) were generated by photolysis of the caged Ca2+ compound nitrophenyl (NP)-EGTA. The evoked RyR activity was measured in planar lipid bilayers in the presence of 0.6-1.3 mM free Mg2+ at the background of 3 mM total ATP in the presence or absence of 1 mM luminal Ca2+. Mg2+ dramatically slowed the rate of activation of RyRs in response to sustained (=" BORDER="0">10-ms) elevations in Ca2+ concentration. Paradoxically, Mg2+ had no measurable impact on the kinetics of the RyR response induced by physiologically relevant, brief (<1-ms) Ca2+ stimuli. Instead, the changes in activation rate observed with sustained stimuli were translated into a drastic reduction in the probability of responses. Luminal Ca2+ did not affect the peak open probability or the probability of responses to brief Ca2+ signals; however, it slowed the transition to steady state and increased the steady-state open probability of the channel. Our results indicate that Mg2+ is a critical physiological determinant of the dynamic behavior of the RyR channel, which is expected to profoundly influence the fidelity of coupling between L-type Ca2+ channels and RyRs in heart cells. excitation-contraction coupling; cardiac myocytes; magnesium; calcium signaling 相似文献
18.
Effects of estradiol on phenylephrine contractility associated with intracellular calcium release in rat aorta 总被引:1,自引:0,他引:1
Castillo C Ceballos G Rodríguez D Villanueva C Medina R López J Méndez E Castillo EF 《American journal of physiology. Cell physiology》2006,291(6):C1388-C1394
The ability of estradiol to affect phenylephrine-induced contraction and the subsequent increase in resting tone, associated with capacitative Ca2+ entry across the plasma membrane, was evaluated in rat aortic rings incubated in Ca2+-free solution. The incubation with estradiol (1100 nM, 5 min) inhibited both the phenylephrine-induced contraction and the IRT. Neither cycloheximide (1 µM; inhibitor of protein synthesis) nor tamoxifen (1 µM; blocker of estrogenic receptors) modified the effects of estradiol. Estradiol (100 µM) also blocked the contractile response to serotonin (10 µM) but not to caffeine (10 mM). In addition, estradiol (100 µM) inhibited the contractile responses to cyclopiazonic acid (1 µM; selective Ca2+-ATPase inhibitor) associated with capacitative Ca2+ influx through non-L-type Ca2+ channels. Finally, estradiol inhibited the Ca2+-induced increases in intracellular free Ca2+ (after pretreatment with phenylephrine) in cultured rat aorta smooth muscle cells incubated in Ca2+-free solution. In conclusion, estradiol interfered in a concentration-dependent manner with Ca2+-dependent contractile effects mediated by the stimuli of 1-adrenergic and serotonergic receptors and inhibited the capacitative Ca2+ influx through both L-type and non-L-type Ca2+ channels. Such effects are in essence nongenomic and not mediated by the intracellular estrogenic receptor. estrogen; 1-adrenergic agonists 相似文献
19.
Su Z Barker DS Csutora P Chang T Shoemaker RL Marchase RB Blalock JE 《American journal of physiology. Cell physiology》2003,284(2):C497-C505
Thecoupling mechanism between depletion of Ca2+ stores in theendoplasmic reticulum and plasma membrane store-operated ion channelsis fundamental to Ca2+ signaling in many cell types and hasyet to be completely elucidated. Using Ca2+release-activated Ca2+ (CRAC) channels in RBL-2H3 cells asa model system, we have shown that CRAC channels are maintained in theclosed state by an inhibitory factor rather than being opened by theinositol 1,4,5-trisphosphate receptor. This inhibitory role can befulfilled by the Drosophila protein INAD (inactivation-noafter potential D). The action of INAD requires Ca2+ andcan be reversed by a diffusible Ca2+ influx factor. Thusthe coupling between the depletion of Ca2+ stores and theactivation of CRAC channels may involve a mammalian homologue of INADand a low-molecular-weight, diffusible store-depletion signal. 相似文献
20.
De Roos Albert D.G.; Willems Peter H.G.M.; Van Zoelen Everardus J.J.; Theuvenet Alexander P.R. 《American journal of physiology. Cell physiology》1997,273(6):C1900
Theintercellular propagation of Ca2+waves by diffusion of inositol trisphosphate has been shown to be ageneral mechanism by which nonexcitable cells communicate. Here, weshow that monolayers of normal rat kidney (NRK) fibroblasts behave likea typical excitable tissue. In confluent monolayers of these cells,Ca2+ action potentials can begenerated by local depolarization of the monolayer on treatment witheither bradykinin or an elevation of the extracellularK+ concentration. Theseelectrotonically propagating action potentials travel intercellularlyover long distances in an all-or-none fashion at a speed of ~6.1 mm/sand can be blocked by L-typeCa2+ channel blockers. The actionpotentials are generated by depolarizations beyond the threshold valuefor L-type Ca2+ channels of about15 mV. The result of these locally induced, propagatingCa2+ action potentials is analmost synchronous, transient increase in the intracellularCa2+ concentration in largenumbers of cells. These data show that electrically coupled fibroblastscan form an excitable syncytium, and they elucidate a novel mechanismof intercellular Ca2+ signaling inthese cells that may coordinate synchronized multicellular responses tolocal stimuli. 相似文献