共查询到20条相似文献,搜索用时 15 毫秒
1.
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
2.
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
3.
Currie KP 《Cellular and molecular neurobiology》2010,30(8):1201-1208
Catecholamines and other transmitters released from adrenal chromaffin cells play central roles in the “fight-or-flight” response
and exert profound effects on cardiovascular, endocrine, immune, and nervous system function. As such, precise regulation
of chromaffin cell exocytosis is key to maintaining normal physiological function and appropriate responsiveness to acute
stress. Chromaffin cells express a number of different G protein coupled receptors (GPCRs) that sense the local environment
and orchestrate this precise control of transmitter release. The primary trigger for catecholamine release is Ca2+ entry through voltage-gated Ca2+ channels, so it makes sense that these channels are subject to complex regulation by GPCRs. In particular G protein βγ heterodimers
(Gβγ) bind to and inhibit Ca2+ channels. Here I review the mechanisms by which GPCRs inhibit Ca2+ channels in chromaffin cells and how this might be altered by cellular context. This is related to the potent autocrine inhibition
of Ca2+ entry and transmitter release seen in chromaffin cells. Recent data that implicate an additional inhibitory target of Gβγ
on the exocytotic machinery and how this might fine tune neuroendocrine secretion are also discussed. 相似文献
4.
Ross WN Nakamura T Watanabe S Larkum M Lasser-Ross N 《Cellular and molecular neurobiology》2005,25(2):283-295
Synaptically activated postsynaptic [Ca2+]i increases occur through three main pathways: Ca2+ entry through voltage-gated Ca2+ channels, Ca2+ entry through ligand-gated channels, and Ca2+ release from internal stores. The first two pathways have been studied intensively; release from stores has been the subject of more recent investigations.Ca2+ release from stores in CNS neurons primarily occurs as a result of IP3 mobilized by activation of metabotropic glutamatergic and/or cholingergic receptors coupled to PLC. Ca2+ release is localized near spines in Purkinje cells and occurs as a wave in the primary apical dendrites of pyramidal cells in the hippocampus and cortex. The amplitude of the [Ca2+]i increase can reach several micromolar, significantly larger than the increase due to backpropagating spikes.The large amplitude, long duration, and unique location of the [Ca2+]i increases due to Ca2+ release from stores suggests that these increases can affect specific downstream signaling mechanisms in neurons. 相似文献
5.
Nicotinic acid dinucleotide phosphate (NAADP) is unique amongst Ca2+ mobilizing messengers in that its principal function is to mobilize Ca2+ from acidic organelles. Early studies indicated that it was likely that NAADP activates a novel Ca2+ release channel distinct from the well characterized Ca2+ release channels on the (sarco)-endoplasmic reticulum (ER), inositol trisphosphate and ryanodine receptors. In this review,
we discuss the emergence of a novel family of endolysosomal channels, the two-pore channels (TPCs), as likely targets for
NAADP, and how molecular and pharmacological manipulation of these channels is enhancing our understanding of the physiological
roles of NAADP as an intracellular Ca2+ mobilizing messenger. 相似文献
6.
Abstract: Morphine-induced release of adenosine from the spinal cord is believed to contribute to spinal antinociception. Although this release is Ca2+ dependent, little is known of the nature of this dependence. In this study, the effects of the dihydropyridine L-type Ca2+ channel agonist Bay K 8644 and the antagonist nifedipine, the N-type Ca2+ channel antagonist ω-conotoxin, and ruthenium red, a blocker of Ca2+ influx induced by capsaicin, on release of adenosine evoked by morphine were determined. The effect of partial depolarization with a minimally effective concentration of K+ on morphine-evoked release of adenosine also was examined. Morphine 10?5-10?4M produced a dose-dependent enhancement of adenosine release from dorsal spinal cord synaptosomes. Following the addition of 6 mM K+ (total K+ concentration of 10.7 mM), 10?6M morphine also enhanced release, and an additional component of action at 10?8M was revealed. Release was Ca2+-dependent as it was not observed in the absence of Ca2+ and presence of EGTA. Bay K 8644 (10 nM) and nifedipine (100 nM) had no effect on the release of adenosine evoked by morphine, but ω-conotoxin (100 nM) markedly reduced such release in both the absence and the presence of the additional 6 mM K+. Morphine-evoked adenosine release was not altered in the presence of a partially effective dose of capsaicin, nor by ruthenium red. These results indicate that morphine can stimulate two distinct phases of adenosine release from the spinal cord (nanomolar and micromolar), and that both phases of release are due to Ca2+ entry via ω-conotoxin-sensitive N-type Ca2+ channels. 相似文献
7.
Ca2+ release from intracellular stores of pig oocytes was investigated using the Ca2+-sensitive fluorescent dye chlorotetracycline. Oocytes were divided into growing ones and those that completed their growth
using brilliant cresyl blue (BCB) staining. The stained oocytes (BCB “+”) were determined as the ones that completed their
growth, while the stainless ones (BCB “−”) were determined as those in the final stages of growth. In the BCB “+” and BCB
“−” oocytes, prolactin, theophylline, GTP, and GDP cause Ca2+ to exit intracellular stores. In the oocytes that completed their growth, joint action of prolactin and GTP activates additional
release of Ca2+, in which protein kinase C takes part. In growing oocytes, joint action of prolactin and GTP does not lead to additional
release of Ca2+. Joint action of theophylline and GDP in growing oocytes and oocytes that completed the growth stage promotes additional
Ca2+ exit from intracellular stores. This exit is regulated by protein kinase A. The obtained data show that there various routes
of Ca2+ release from intracellular stores in growing and grown pig oocytes. 相似文献
8.
Relevant Ca2+ pools and fluxes in H9c2 cells have been studied using fluorescent indicators and Ca2+-mobilizing agents. Vasopressin produced a cytoplasmic Ca2+ peak with half-maximal effective concentration of 6 nM, whereas thapsigargin-induced Ca2+ increase showed half-maximal effect at 3 nM. Depolarization of the mitochondrial inner membrane by protonophore was also associated with an increase in cytoplasmic Ca2+. Ionomycin induced a small and sustained depolarization, while thapsigargin had a small but transient effect. The thapsigargin-sensitive Ca2+ pool was also sensitive to ionomycin, whereas the protonophore-sensitive Ca2+ pool was not. The vasopressin-induced cytoplasmic Ca2+ signal, which caused a reversible discharge of the sarco-endoplasmic reticulum Ca2+ pool, was sensed as a mitochondrial Ca2+ peak but was unaffected by the permeability transition pore inhibitor cyclosporin A. The mitochondrial Ca2+ peak was affected by cyclosporin A when the Ca2+ signal was induced by irreversible discharge of the intracellular Ca2+ pool, i.e., adding thapsigargin. These observations indicate that the mitochondria interpret the cytoplasmic Ca2+ signals generated in the reticular store. 相似文献
9.
SantoDomingo J Fonteriz RI Lobatón CD Montero M Moreno A Alvarez J 《Cellular and molecular neurobiology》2010,30(8):1267-1274
We have investigated the dynamics of the free [Ca2+] inside the secretory granules of neurosecretory PC12 and INS1 cells using a low-Ca2+-affinity aequorin chimera fused to synaptobrevin-2. The steady-state secretory granule [Ca2+] ([Ca2+]SG] was around 20–40 μM in both cell types, about half the values previously found in chromaffin cells. Inhibition of SERCA-type
Ca2+ pumps with thapsigargin largely blocked Ca2+ uptake by the granules in Ca2+-depleted permeabilized cells, and the same effect was obtained when the perfusion medium lacked ATP. Consistently, the SERCA-type
Ca2+ pump inhibitor benzohydroquinone induced a rapid release of Ca2+ from the granules both in intact and permeabilized cells, suggesting that the continuous activity of SERCA-type Ca2+ pumps is essential to maintain the steady-state [Ca2+]SG. Both inositol 1,4,5-trisphosphate (InsP3) and caffeine produced a rapid Ca2+ release from the granules, suggesting the presence of InsP3 and ryanodine receptors in the granules. The response to high-K+ depolarization was different in both cell types, a decrease in [Ca2+]SG in PC12 cells and an increase in [Ca2+]SG in INS1 cells. The difference may rely on the heterogeneous response of different vesicle populations in each cell type.
Finally, increasing the glucose concentration triggered a decrease in [Ca2+]SG in INS1 cells. In conclusion, our data show that the secretory granules of PC12 and INS1 cells take up Ca2+ through SERCA-type Ca2+ pumps and can release it through InsP3 and ryanodine receptors, supporting the hypothesis that secretory granule Ca2+ may be released during cell stimulation and contribute to secretion. 相似文献
10.
Do Han Kim Frank A. Sreter S.Tsuyoshi Ohnishi John F. Ryan James Roberts Paul D. Allen Laszlo G. Meszaros Bozena Antoniu Noriaki Ikemoto 《生物化学与生物物理学报:生物膜》1984,775(3):320-327
The time-course of Ca2+ release from sarcoplasmic reticulum isolated from muscles of normal pigs and those of pigs susceptible to malignant hyperthermia were investigated using stopped-flow spectrophotometry and arsenazo III as a Ca2+ indicator. Several methods were used to trigger Ca2+ release: (a) addition of halothane (e.g., 0.2 mM); (b) an increase of extravesicular Ca2+ concentration ([Ca02+]); (c) a combination of (a) and (b), and (d) replacement of ions (potassium gluconate with choline chloride) to produce membrane depolarization. The initial rates of Ca2+ release induced by either halothane or Ca2+ alone, or both, are at least 70% higher in malignant hyperthermic sarcoplasmic reticulum than in normal. The amount of Ca2+ released by halothane at low [Ca02+] in malignant hyperthermic sarcoplasmic reticulum is about twice as large as in normal sarcoplasmic reticulum. Membrane depolarization led to biphasic Ca2+ release in both malignant hyperthermic and normal sarcoplasmic reticulum, the rate constant of the rapid phase of Ca2+ release induced by membrane depolarization being significantly higher in malignant hyperthermic sarcoplasmic reticulum () than in normal (). Thus, all types of Ca2+ release investigated (a, b, c and d) have higher rates in malignant hyperthermic sarcoplasmic reticulum than normal sarcoplasmic reticulum. These results suggest that the putative Ca2+ release channels located in the sarcoplasmic reticulum are altered in malignant hyperthermic sarcoplasmic reticulum. 相似文献
11.
A mathematical modeling of tight junction (TJ) dynamics was elaborated in a previous study (Kassab, F., Marques, R.P., Lacaz-Vieira, F. 2002. Modeling tight junction dynamics and oscillations. J. Gen. Physiol. 120:237–247) to better understand the dynamics of TJ opening and closing, as well as oscillations of TJ permeability that are observed in response to changes of extracellular Ca2+ levels. In this model, TJs were assumed to be specifically controlled by the Ca2+ concentration levels at the extracellular Ca2+ binding sites of zonula adhaerens. Despite the fact that the model predicts all aspects of TJ dynamics, we cannot rule out the likelihood that changes of intracellular Ca2+ concentration (Ca2+ cell), which might result from changes \ of extracellular Ca2+ concentration (Ca2+ extl), contribute to the observed results. In order to address this aspect of TJ regulation, fast Ca2+-switch experiments were performed in which changes of Ca2+ cell were induced using the Ca2+ ionophore A23187 or thapsigargin, a specific inhibitor of the sarco-endoplasmic reticulum Ca2+-ATPase. The results indicate that the ionophore or thapsigargin per se do not affect basal tissue electrical conductance (G), showing that the sealing of TJs is not affected by a rise in Ca2+ cell. When TJs were kept in a dynamic state, as partially open structures or in oscillation, conditions in which the junctions are very sensitive to disturbances that affect their regulation, a rise of Ca2+ cell never led to a decline of G, indicating that a rise of Ca2+ cell does not trigger per se TJ closure. On the contrary, always the first response to a rise of Ca2+ cell is an increase of G that, in most cases, is a transient response. Despite these observations we cannot assure that a rise of Ca2+ cell is without effect on the TJs, since an increase of Ca2+ cell not only causes a transient increase of G but, in addition, during oscillations a rise of Ca2+ cell induced by the Ca2+ ionophore transiently halted the oscillatory pattern of TJs. The main conclusion of this study is that TJ closure that is observed when basolateral Ca2+ concentration (Ca2+ bl) is increased after TJs were opened by Ca2+ bl removal cannot be ascribed to a rise of Ca2+ cell and might be a consequence of Ca2+ binding to extracellular Ca2+ sites. 相似文献
12.
Ion channels are targets of various antiepileptic drugs. In cerebral presynaptic nerve endings Na+ and Ca2+ channels are particularly abundant, as they control neurotransmitter release, including the release of glutamate (Glu), the most concentrated excitatory amino acid neurotransmitter in the brain. Several pre-synaptic channels are implicated in the mechanism of action of the pro-convulsive agent, 4-aminopyridine (4-AP). In the present study the effects of levetiracetam and other established and newer (vinpocetine) anti-epileptic drugs, as well as of the anti-depressant, sertraline on the increase in Ca2+ induced by 4-AP in hippocampal isolated nerve endings were investigated. Also the effects of some of the anti-seizure drugs on the selective increase in Ca2+ induced by high K+, or on the selective increase in Na+ induced by veratridine were tested. Sertraline and vinpocetine effectively inhibited the rise in Ca2+ induced by 4-AP, which was dependent on the out-in Na+ gradient and tetrodotoxin sensitive. Carbamazepine, phenytoin, lamotrigine and oxcarbazepine inhibited the rise in Ca2+ induced by 4-AP too, but at higher concentrations than sertraline and vinpocetine, whereas levetiracetam, valproic acid and topiramate did not. The three latter antiepileptic drugs also failed in modifying other responses mediated by the activation of brain presynaptic Na+ or Ca2+ channels, including Glu release. This indicates that levetiracetam, valproic acid and topiramate mechanisms of action are unrelated with a decrease in presynaptic Na+ or Ca2+ channels permeability. It is concluded that depolarized cerebral isolated nerve endings represent a useful tool to unmask potential antiepileptic drugs targeting presynaptic Na+ and/or Ca2+ channels in the brain; such as vinpocetine or the anti-depressant sertraline, which high effectiveness to control seizures in the animal in vivo has been demonstrated. 相似文献
13.
Elzbieta Zieminska Jacek Lenart Dominik Diamandakis Jerzy W. Lazarewicz 《Neurochemical research》2017,42(3):777-787
Using primary cultures of rat cerebellar granule cells (CGC) we examined the role of calcium transients induced by tetrabromobisphenol A (TBBPA) in triggering oxidative stress and cytotoxicity. CGC were exposed for 30 min to 10 or 25 µM TBBPA. Changes in intracellular calcium concentration ([Ca2+]i), in the production of reactive oxygen species (ROS), and in the potential of mitochondria (?Ψm) were measured fluorometrically during the exposure. The intracellular glutathione (GSH) and catalase activity were determined after the incubation; cell viability was evaluated 24 h later. TBBPA concentration-dependently increased [Ca2+]i and ROS production, and reduced GSH content, catalase activity, ?Ψm and neuronal viability. The combination of NMDA and ryanodine receptor antagonists, MK-801 and bastadin 12 with ryanodine, respectively, prevented Ca2+ transients and partially reduced cytotoxicity induced by TBBPA at both concentrations. The antagonists also completely inhibited oxidative stress and depolarization of mitochondria evoked by 10 µM TBBPA, whereas these effects were only partially reduced in the 25 µM TBBPA treatment. Free radical scavengers prevented TBBPA-induced development of oxidative stress and improved CGC viability without having any effect on the rises in Ca2+ and drop in ?Ψm. The co-administration of scavengers with NMDA and ryanodine receptor antagonists provided almost complete neuroprotection. These results indicate that Ca2+ imbalance and oxidative stress both mediate acute toxicity of TBBPA in CGC. At 10 µM TBBPA Ca2+ imbalance is a primary event, inducing oxidative stress, depolarization of mitochondria and cytotoxicity, whilst at a concentration of 25 µM TBBPA an additional Ca2+-independent portion of oxidative stress and cytotoxicity emerges. 相似文献
14.
The effects of guanine nucleotides and protein kinase C on prolactin-stimulated Ca2+ release from intracellular stores of pig oocytes were studied using the fluorescent dye chlorotetracycline. The effect of prolactin was related to the protein kinase C activation. Inhibition of protein kinase C stimulated Ca2+ release from intracellular stores of the pig oocytes treated with 5 ng/ml prolactin in the presence of extracellular Ca2+ and inhibited Ca2+ release from intracellular stores of the pig oocytes treated with 50 ng/ml prolactin. In a Ca2+-free medium, prolactin did not stimulate Ca2+ release from intracellular stores of the oocytes treated with GDP in the presence of GDP. GTP inhibition of protein kinase C activated Ca2+ release from intracellular stores of the pig oocytes treated with 5 ng/ml prolactin and inhibited Ca2+ release from intracellular stores of the pig oocytes treated with 50 ng/ml prolactin. These data suggest the influence of guanine nucleotides and protein kinase C on calcium metabolism, stimulated by prolactin.__________Translated from Ontogenez, Vol. 36, No. 3, 2005, pp. 199–204.Original Russian Text Copyright © 2005 by Denisenko, Kuzmina. 相似文献
15.
Activation of acetylcholine receptors (AChR) triggers catecholamine release from adrenal chromaffin cells and release of neurotransmitters in neuron-to-neuron and neuromuscular junctions, including those on smooth muscle cells. Calcium ions play the role of the main intracellular messenger, which mediates these processes. In our study, we explored the properties of Ca2+ signaling triggered by activation of AChR by analyzing the characteristics of Ca2+ transients induced by selective activation of nicotinic (nAChR) and muscarinic (mAChR) cholinoreceptors using Fura-2 fluorescent measurements in experiments on rat chromaffin cells. Two populations of chromaffin cells, which in a different manner responded to AChR stimulation, were classified. We found that the mean frequency of quantum release induced by ACh is considerably higher than that during hyperpotassium cell depolarization. Comparative analysis of single secretory events showed that, in the case of stimulation by ACh, single secretory spikes demonstrate faster kinetic characteristics than those induced by depolarization. Statistical analysis of the integral magnitude (area) of single secretory spikes evoked by both types of stimulation showed no significant difference despite amplitude and kinetic dissimilarities between such secretory events. Mathematical modeling of the dynamics of the exocytotic processes led to the conclusion that the reason for the specific kinetic characteristics of single secretory responses may be different diameters of the secretory pores formed during fusion of secretory vesicles with the plasma membrane. 相似文献
16.
Persistent Enhancement of Sustained Calcium-Dependent Glutamate Release by Phorbol Esters: Requirement for Localized Calcium Entry 总被引:3,自引:0,他引:3
David M. Terrian 《Journal of neurochemistry》1995,64(1):172-180
Abstract: Sustained activation of protein kinase C significantly enhanced a secondary (slow) phase in the depolarization-induced release of glutamate from isolated hippocampal nerve endings. The phorbol ester, 4β-phorbol 12,13-dibutyrate, was used to sustain the activation of presynaptic protein kinase C for a prolonged (10-min) period, and then this relatively water-soluble phorbol ester was removed by superfusion before a 2-min stimulus of continuous membrane depolarization. These conditions were used to investigate the persistent effects of sustained protein kinase C activation on the magnitude of the slow phase of evoked glutamate release, in which the efficiency of synaptic vesicle mobilization and recycling may be primary determinants of response magnitude. It is reported here that sustained protein kinase C activation selectively increased the Ca2+-dependent component of glutamate release during a prolonged phase of K+-induced depolarization. The magnitude of this persistent effect on Ca2+-dependent glutamate release was directly related to the dose of 4β-phorbol 12,13-dibutyrate and the duration of exposure that was used to prime the release apparatus, was observed using two alternative synaptosomal preparations, and was evident regardless of the depolarizing stimulus used (elevated [KCl] or 4-aminopyridine). However, 4β-phorbol 12,13-dibutyrate did not alter the release induced by the Ca2+ ionophore ionomycin. Thus, the persistent effects of protein kinase C activation on a prolonged phase of glutamate release were dependent on the route of Ca2+ influx. The finding that voltage-regulated Ca2+ channel blockers were able to neutralize completely the 4β-phorbol 12,13-dibutyrate-dependent facilitation of K+-evoked glutamate release provided further support for this conclusion. Thus, 4β-phorbol 12,13-dibutyrate significantly potentiated the sustained release of glutamate without altering the strict requirement that is normally displayed by synaptosomes for localized and voltage-regulated Ca2+ entry. 相似文献
17.
Parallel computation employing a domain decomposition method was used to calculate precisely without approximations the spatio-temporal distribution of Ca2+ in nerve terminals. The results showed, contrary to expectations, that for equal admitted Ca2+ currents at low (one channel open) and high (four channels open) depolarization, the average Ca2+ concentration at the release area is higher at the low depolarization. These calculations provide additional support for the Ca2+-voltage hypothesis for neurotransmitter release. 相似文献
18.
Maria Teresa Alonso Maria José Barrero Pedro Michelena Estela Carnicero Inmaculada Cuchillo Antonio G. García Javier García-Sancho Mayte Montero Javier Alvarez 《The Journal of cell biology》1999,144(2):241-254
The presence and physiological role of Ca2+-induced Ca2+ release (CICR) in nonmuscle excitable cells has been investigated only indirectly through measurements of cytosolic [Ca2+] ([Ca2+]c). Using targeted aequorin, we have directly monitored [Ca2+] changes inside the ER ([Ca2+]ER) in bovine adrenal chromaffin cells. Ca2+ entry induced by cell depolarization triggered a transient Ca2+ release from the ER that was highly dependent on [Ca2+]ER and sensitized by low concentrations of caffeine. Caffeine-induced Ca2+ release was quantal in nature due to modulation by [Ca2+]ER. Whereas caffeine released essentially all the Ca2+ from the ER, inositol 1,4,5-trisphosphate (InsP3)- producing agonists released only 60–80%. Both InsP3 and caffeine emptied completely the ER in digitonin-permeabilized cells whereas cyclic ADP-ribose had no effect. Ryanodine induced permanent emptying of the Ca2+ stores in a use-dependent manner after activation by caffeine. Fast confocal [Ca2+]c measurements showed that the wave of [Ca2+]c induced by 100-ms depolarizing pulses in voltage-clamped cells was delayed and reduced in intensity in ryanodine-treated cells. Our results indicate that the ER of chromaffin cells behaves mostly as a single homogeneous thapsigargin-sensitive Ca2+ pool that can release Ca2+ both via InsP3 receptors or CICR. 相似文献
19.
Derek R. Laver 《Biophysical reviews》2018,10(4):1087-1095
Ryanodine receptors (RyRs) are the Ca2+ release channels in the sarcoplasmic reticulum in striated muscle which play an important role in excitation-contraction coupling and cardiac pacemaking. Single channel recordings have revealed a wealth of information about ligand regulation of RyRs from mammalian skeletal and cardiac muscle (RyR1 and RyR2, respectively). RyR subunit has a Ca2+ activation site located in the luminal and cytoplasmic domains of the RyR. These sites synergistically feed into a common gating mechanism for channel activation by luminal and cytoplasmic Ca2+. RyRs also possess two inhibitory sites in their cytoplasmic domains with Ca2+ affinities of the order of 1 μM and 1 mM. Magnesium competes with Ca2+ at these sites to inhibit RyRs and this plays an important role in modulating their Ca2+-dependent activity in muscle. This review focuses on how these sites lead to RyR modulation by Ca2+ and Mg2+ and how these mechanisms control Ca2+ release in excitation-contraction coupling and cardiac pacemaking. 相似文献
20.
The interaction between prolactin and theophylline as well as between prolactin and guanosine triphosphate during Ca2+ release from intracellular stores of estradiol-treated porcine oocytes isolated from the ovary at the stage of follicular growth were studied using fluorescent Ca2+-sensitive probe chlortetracycline. In the absence of estradiol, prolactin or theophylline induced Ca2+ release from intracellular stores; however, no increase in Ca2+ release was observed after their combined action. Conversely, Ca2+ release from intracellular stores increased only after the combined exposure to prolactin and theophylline in the presence of estradiol. In the absence of estradiol, guanosine triphosphate induced calcium release alone and together with prolactin. Protein kinase C regulated Ca2+ release from intracellular stores after the combined exposure to prolactin and theophylline only in the presence of estradiol; while the activation of protein kinase C required no estradiol during the combined exposure to prolactin and guanosine triphosphate. The data obtained indicate the effect of estradiol on Ca2+ release from intracellular stores after the combined exposure to prolactin and theophylline, while no such effect was observed after the combined exposure to prolactin and guanosine triphosphate. 相似文献