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1.
Merkel cells (MCs) associated with nerve terminals constitute MC-neurite complexes, which are involved in slowly-adapting type I mechanoreception. Although MCs are known to express voltage-gated Ca 2+ channels and hypotonic-induced membrane deformation is known to lead to Ca 2+ transients, whether MCs initiate mechanotransduction is currently unknown. To answer to this question, rat MCs were transfected with a reporter vector, which enabled their identification. Their properties were investigated through electrophysiological studies. Voltage-gated K +, Ca 2+ and Ca 2+-activated K + (K Ca) channels were identified, as previously described. Here, we also report the activation of Ca 2+ channels by histamine and their inhibition by acetylcholine. As a major finding, we demonstrated that direct mechanical stimulations induced strong inward Ca 2+ currents in MCs. Depolarizations were dependent on the strength and the length of the stimulation. Moreover, touch-evoked currents were inhibited by the stretch channel antagonist gadolinium. These data confirm the mechanotransduction capabilities of MCs. Furthermore, we found that activation of the osmoreceptor TRPV4 in FM1-43-labeled MCs provoked neurosecretory granule exocytosis. Since FM1-43 blocks mechanosensory channels, this suggests that hypo-osmolarity activates MCs in the absence of mechanotransduction. Thus, mechanotransduction and osmoreception are likely distinct pathways. 相似文献
2.
Lysosomes are considered to be a terminal degradative compartment of the endocytic pathway, into which transport is mostly unidirectional. However, specialized secretory vesicles regulated by Ca 2+, such as neutrophil azurophil granules, mast cell–specific granules, and cytotoxic lymphocyte lytic granules, share characteristics with lysosomes that may reflect a common biogenesis. In addition, the involvement of Ca 2+ transients in the invasion mechanism of the parasite Trypanosoma cruzi, which occurs by fusion of lysosomes with the plasma membrane, suggested that lysosome exocytosis might be a generalized process present in most cell types. Here we demonstrate that elevation in the intracellular free Ca2+ concentration of normal rat kidney (NRK) fibroblasts induces fusion of lysosomes with the plasma membrane. This was verified by measuring the release of the lysosomal enzyme β-hexosaminidase, the appearance on the plasma membrane of the lysosomal glycoprotein lgp120, the release of fluid-phase tracers previously loaded into lysosomes, and the release of the lysosomally processed form of cathepsin D. Exposure to the Ca2+ ionophore ionomycin or addition of Ca2+containing buffers to streptolysin O–permeabilized cells induced exocytosis of ~10% of the total lysosomes of NRK cells. The process was also detected in other cell types such as epithelial cells and myoblasts. Lysosomal exocytosis was found to require micromolar levels of Ca2+ and to be temperature and ATP dependent, similar to Ca2+-regulated secretory mechanisms in specialized cells. These findings highlight a novel role for lysosomes in cellular membrane traffic and suggest that fusion of lysosomes with the plasma membrane may be an ubiquitous form of Ca2+-regulated exocytosis. 相似文献
3.
BackgroundThe global disparity in cancer incidence remains a major public health problem. We focused on prostate cancer since microscopic disease in men is common, but the incidence of clinical disease varies more than 100 fold worldwide. Ca 2+ signaling is a central regulator of cell proliferation, but has received little attention in cancer prevention. We and others have reported a strong dose-dependent reduction in the incidence of prostate and lung cancer within populations exposed to boron (B) in drinking water and food; and in tumor and cell proliferation in animal and cell culture models. Methods/Principal FindingsWe examined the impact of B on Ca 2+ stores using cancer and non-cancer human prostate cell lines, Ca 2+ indicators Rhod-2 AM and Indo-1 AM and confocal microscopy. In DU-145 cells, inhibition of Ca 2+ release was apparent following treatment with Ringers containing RyR agonists cADPR, 4CmC or caffeine and respective levels of BA (50 µM), (1, 10 µM) or (10, 20, 50,150 µM). Less aggressive LNCaP cancer cells required 20 µM BA and the non-tumor cell line PWR1E required 150 µM BA to significantly inhibit caffeine stimulated Ca 2+ release. BA (10 µM) and the RyR antagonist dantroline (10 µM) were equivalent in their ability to inhibit ER Ca 2+ loss. Flow cytometry and confocal microscopy analysis showed exposure of DU-145 cells to 50 µM BA for 1 hr decreased stored [Ca 2+] by 32%. Conclusion/SignificanceWe show B causes a dose dependent decrease of Ca 2+ release from ryanodine receptor sensitive stores. This occurred at BA concentrations present in blood of geographically disparate populations. Our results suggest higher BA blood levels lower the risk of prostate cancer by reducing intracellular Ca 2+ signals and storage. 相似文献
4.
Cysteine string protein (Csp) is essential for neurotransmitter release in Drosophila. It has been suggested that Csp functions by regulating the activity of presynaptic Ca 2+ channels, thus controlling exocytosis. We have examined the effect of overexpressing Csp1 in PC12 cells, a neuroendocrine cell line. PC12 cell clones overexpressing Csp1 did not show any changes in morphology, granule number or distribution, or in the levels of other key exocytotic proteins. This overexpression did not affect intracellular Ca 2+ signals after depolarization, suggesting that Csp1 has no gross effect on Ca 2+ channel activity in PC12 cells. In contrast, we show that Csp1 overexpression enhances the extent of exocytosis from permeabilized cells in response to Ca 2+ or GTPγS in the absence of Ca 2+. Because secretion from permeabilized cells is not influenced by Ca 2+ channel activity, this represents the first demonstration that Csp has a direct role in regulated exocytosis. 相似文献
5.
Glucagon, secreted from pancreatic islet α cells, stimulates gluconeogenesis and liver glycogen breakdown. The mechanism regulating glucagon release is debated, and variously attributed to neuronal control, paracrine control by neighbouring β cells, or to an intrinsic glucose sensing by the α cells themselves. We examined hormone secretion and Ca 2+ responses of α and β cells within intact rodent and human islets. Glucose-dependent suppression of glucagon release persisted when paracrine GABA or Zn 2+ signalling was blocked, but was reversed by low concentrations (1–20 μM) of the ATP-sensitive K + (K ATP) channel opener diazoxide, which had no effect on insulin release or β cell responses. This effect was prevented by the K ATP channel blocker tolbutamide (100 μM). Higher diazoxide concentrations (≥30 μM) decreased glucagon and insulin secretion, and α- and β-cell Ca 2+ responses, in parallel. In the absence of glucose, tolbutamide at low concentrations (<1 μM) stimulated glucagon secretion, whereas high concentrations (>10 μM) were inhibitory. In the presence of a maximally inhibitory concentration of tolbutamide (0.5 mM), glucose had no additional suppressive effect. Downstream of the K ATP channel, inhibition of voltage-gated Na + (TTX) and N-type Ca 2+ channels (ω-conotoxin), but not L-type Ca 2+ channels (nifedipine), prevented glucagon secretion. Both the N-type Ca 2+ channels and α-cell exocytosis were inactivated at depolarised membrane potentials. Rodent and human glucagon secretion is regulated by an α-cell K ATP channel-dependent mechanism. We propose that elevated glucose reduces electrical activity and exocytosis via depolarisation-induced inactivation of ion channels involved in action potential firing and secretion. 相似文献
6.
In Paramecium tetraurelia, polyamine-triggered exocytosis is accompanied by the activation of Ca 2+-activated currents across the cell membrane (Erxleben, C., and H. Plattner. 1994. J. Cell Biol. 127:935– 945). We now show by voltage clamp and extracellular recordings that the product of current × time (As) closely parallels the number of exocytotic events. We suggest that Ca 2+ mobilization from subplasmalemmal storage compartments, covering almost the entire cell surface, is a key event. In fact, after local stimulation, Ca 2+ imaging with high time resolution reveals rapid, transient, local signals even when extracellular Ca 2+ is quenched to or below resting intracellular Ca 2+ concentration ([Ca 2+] e [Ca 2+] i). Under these conditions, quenched-flow/freeze-fracture analysis shows that membrane fusion is only partially inhibited. Increasing [Ca 2+] e alone, i.e., without secretagogue, causes rapid, strong cortical increase of [Ca 2+] i but no exocytosis. In various cells, the ratio of maximal vs. minimal currents registered during maximal stimulation or single exocytotic events, respectively, correlate nicely with the number of Ca stores available. Since no quantal current steps could be observed, this is again compatible with the combined occurrence of Ca 2+ mobilization from stores (providing close to threshold Ca 2+ levels) and Ca 2+ influx from the medium (which per se does not cause exocytosis). This implies that only the combination of Ca 2+ flushes, primarily from internal and secondarily from external sources, can produce a signal triggering rapid, local exocytotic responses, as requested for Paramecium defense. 相似文献
7.
Anoxia induces a rapid elevation of the cytosolic Ca 2+ concentration ([Ca 2+] cyt) in maize ( Zea mays L.) cells, which is caused by the release of the ion from intracellular stores. This anoxic Ca 2+ release is important for gene activation and survival in O 2-deprived maize seedlings and cells. In this study we examined the contribution of mitochondrial Ca 2+ to the anoxic [Ca 2+] cyt elevation in maize cells. Imaging of intramitochondrial Ca 2+ levels showed that a majority of mitochondria released their Ca 2+ in response to anoxia and took up Ca 2+ upon reoxygenation. We also investigated whether the mitochondrial Ca 2+ release contributed to the increase in [Ca 2+] cyt under anoxia. Analysis of the spatial association between anoxic [Ca 2+] cyt changes and the distribution of mitochondrial and other intracellular Ca 2+ stores revealed that the largest [Ca 2+] cyt increases occurred close to mitochondria and away from the tonoplast. In addition, carbonylcyanide p-trifluoromethoxyphenyl hydrazone treatment depolarized mitochondria and caused a mild elevation of [Ca 2+] cyt under aerobic conditions but prevented a [Ca 2+] cyt increase in response to a subsequent anoxic pulse. These results suggest that mitochondria play an important role in the anoxic elevation of [Ca 2+] cyt and participate in the signaling of O 2 deprivation. 相似文献
9.
Calcium deficiency causes abnormal colonic growth and increases colon cancer risk with poorly understood mechanisms. Here we elucidate a novel signaling mechanism underlying the Ca 2+ deficiency-induced epithelial proliferation using a unique animal model. The zebrafish larval yolk sac skin contains a group of Ca 2+-transporting epithelial cells known as ionocytes. Their number and density increases dramatically when acclimated to low [Ca 2+] environments. BrdU pulse-labeling experiments suggest that low [Ca 2+] stimulates pre-existing ionocytes to re-enter the cell cycle. Low [Ca 2+] treatment results in a robust and sustained activation of IGF1R-PI3K-Akt signaling in these cells exclusively. These ionocytes specifically express Igfbp5a, a high-affinity and specific binding protein for insulin-like growth factors (IGFs) and the Ca 2+-selective channel Trpv5/6. Inhibition or knockdown of Igfbp5a, IGF1 receptor, PI3K, and Akt attenuates low [Ca 2+]-induced ionocyte proliferation. The role of Trpv5/6 was investigated using a genetic mutant, targeted knockdown, and pharmacological inhibition. Loss-of-Trpv5/6 function or expression results in elevated pAkt levels and increased ionocyte proliferation under normal [Ca 2+]. These increases are eliminated in the presence of an IGF1R inhibitor, suggesting that Trpv5/6 represses IGF1R-PI3K-Akt signaling under normal [Ca 2+]. Intriguingly, blockade of Trpv5/6 activity inhibits the low [Ca 2+]-induced activation of Akt. Mechanistic analyses reveal that the low [Ca 2+]-induced IGF signaling is mediated through Trpv5/6-associated membrane depolarization. Low extracellular [Ca 2+] results in a similar amplification of IGF-induced PI3K-PDK1-Akt signaling in human colon cancer cells in a TRPV6-dependent manner. These results uncover a novel and evolutionarily conserved signaling mechanism that contributes to the abnormal epithelial proliferation associated with Ca 2+ deficiency. 相似文献
10.
AimNeurotransmitter release is elicited by an elevation of intracellular Ca 2+ concentration ([Ca 2+] i). The action potential triggers Ca 2+ influx through Ca 2+ channels which causes local changes of [Ca 2+] i for vesicle release. However, any direct role of extracellular Ca 2+ (besides Ca 2+ influx) on Ca 2+-dependent exocytosis remains elusive. Here we set out to investigate this possibility on rat dorsal root ganglion (DRG) neurons and chromaffin cells, widely used models for studying vesicle exocytosis. ResultsUsing photolysis of caged Ca 2+ and caffeine-induced release of stored Ca 2+, we found that extracellular Ca 2+ inhibited exocytosis following moderate [Ca 2+] i rises (2–3 µM). The IC 50 for extracellular Ca 2+ inhibition of exocytosis (ECIE) was 1.38 mM and a physiological reduction (∼30%) of extracellular Ca 2+ concentration ([Ca 2+] o) significantly increased the evoked exocytosis. At the single vesicle level, quantal size and release frequency were also altered by physiological [Ca 2+] o. The calcimimetics Mg 2+, Cd 2+, G418, and neomycin all inhibited exocytosis. The extracellular Ca 2+-sensing receptor (CaSR) was not involved because specific drugs and knockdown of CaSR in DRG neurons did not affect ECIE. Conclusion/SignificanceAs an extension of the classic Ca 2+ hypothesis of synaptic release, physiological levels of extracellular Ca 2+ play dual roles in evoked exocytosis by providing a source of Ca 2+ influx, and by directly regulating quantal size and release probability in neuronal cells. 相似文献
11.
Ca 2+-dependent exocytotic pathways in mouse pancreatic β cells were investigated using both capacitance measurement and amperometric detection of vesicular contents. Serotonin was preloaded into large dense-core vesicles for the amperometry. Exocytosis was induced by rapid elevation of cytosolic Ca 2+ concentrations using caged-Ca 2+ compounds. Capacitance measurement revealed two major components of exocytosis, and only the slow component was accompanied by amperometric events reflecting quantal serotonin secretion. Moreover, the fast and slow exocytoses induced the two forms of endocytosis that were reported to follow the exocytoses of small-clear and large dense-core vesicles, respectively. Interestingly, we recorded two types of responses of quantal events: in the type-1 response, most quantal events occurred with a delay of 0.2 s and were rapidly exhausted with a time constant of 1.7 s, while, in the type-2 response, quantal events occurred with a delay of 2.5 s and were sustained. This suggests the existence of two pathways or modes of the exocytosis involving large dense-core vesicles. Thus, we have revealed three exocytotic pathways with divergent fusion kinetics in β cells, which provide a new basis for the understanding of the physiology and pathology of β cells. 相似文献
12.
TRPC3 (or Htrp3) is a human member of the trp family of Ca 2+-permeable cation channels. Since expression of TRPC3 cDNA results in markedly enhanced Ca 2+ influx in response to stimulation of membrane receptors linked to phospholipase C (Zhu, X., J. Meisheng, M. Peyton, G. Bouley, R. Hurst, E. Stefani, and L. Birnbaumer. 1996. Cell. 85:661–671), we tested whether TRPC3 might represent a Ca 2+ entry pathway activated as a consequence of depletion of intracellular calcium stores. CHO cells expressing TRPC3 after intranuclear injection of cDNA coding for TRPC3 were identified by fluorescence from green fluorescent protein. Expression of TRPC3 produced cation currents with little selectivity for Ca 2+ over Na +. These currents were constitutively active, not enhanced by depletion of calcium stores with inositol-1,4,5-trisphosphate or thapsigargin, and attenuated by strong intracellular Ca 2+ buffering. Ionomycin led to profound increases of currents, but this effect was strictly dependent on the presence of extracellular Ca 2+. Likewise, infusion of Ca 2+ into cell through the patch pipette increased TRPC3 currents. Therefore, TRPC3 is stimulated by a Ca 2+-dependent mechanism. Studies on TRPC3 in inside-out patches showed cation-selective channels with 60-pS conductance and short (<2 ms) mean open times. Application of ionomycin to cells increased channel activity in cell-attached patches. Increasing the Ca 2+ concentration on the cytosolic side of inside-out patches (from 0 to 1 and 30 μM), however, failed to stimulate channel activity, even in the presence of calmodulin (0.2 μM). We conclude that TRPC3 codes for a Ca 2+-permeable channel that supports Ca 2+-induced Ca 2+-entry but should not be considered store operated. 相似文献
13.
Ca 2+ sparks are the elementary release events in many types of cells. Here we present a morphometric analysis of Ca 2+ sparks (i.e., amplitude and kinetic parameters) using an approach that minimizes the confounding factor of the detection of out-of-focus events. By activation and visualization of Ca 2+ sparks from Ca 2+ release units under loose-seal patch-clamp conditions, we found that the amplitude and rising rate of in-focus sparks exhibited a broad modal distribution, whereas spark rise time and spatial width appeared to be stereotyped. Spark morphometrics were constant irrespective of the latency of spark production and the time-dependent L-type Ca 2+ channel activation. Polymorphism of Ca 2+ sparks in terms of variable amplitude and rising rate was evident for events from the same release units, and intra- and interrelease unit variability contributed equally to the overall variability. The rising rate, a reporter of the underlying Ca 2+ release flux, displayed a strong positive correlation with spark amplitude, but a negative correlation with spark rise time, an index of Ca 2+ release duration. On the basis of Ca 2+ spark morphometrics measured here, we suggested a model in which cohorts of variable number of ryanodine receptors are activated in the genesis of Ca 2+ sparks, and the ensuing negative feedback overrides the regenerative Ca 2+-induced Ca 2+ release to extinguish the ongoing Ca 2+ spark. 相似文献
14.
Two recombinant aequorin isoforms with different Ca 2+ affinities, specifically targeted to the endoplasmic reticulum (ER), were used in parallel to investigate free Ca 2+ homeostasis in the lumen of this organelle. Here we show that, although identically and homogeneously distributed in the ER system, as revealed by both immunocytochemical and functional evidence, the two aequorins measured apparently very different concentrations of divalent cations ([Ca 2+] er or [Sr 2+] er). Our data demonstrate that this contradiction is due to the heterogeneity of the [Ca 2+] of the aequorin-enclosing endomembrane system. Because of the characteristics of the calibration procedure used to convert aequorin luminescence into Ca 2+ concentration, the [Ca 2+] er values obtained at steady state tend, in fact, to reflect not the average ER values, but those of one or more subcompartments with lower [Ca 2+]. These subcompartments are not generated artefactually during the experiments, as revealed by the dynamic analysis of the ER structure in living cells carried out by means of an ER-targeted green fluorescent protein. When the problem of ER heterogeneity was taken into account (and when Sr 2+ was used as a Ca 2+ surrogate), the bulk of the organelle was shown to accumulate free [cation 2+] er up to a steady state in the millimolar range. A theoretical model, based on the existence of multiple ER subcompartments of high and low [Ca 2+], that closely mimics the experimental data obtained in HeLa cells during accumulation of either Ca 2+ or Sr 2+, is presented. Moreover, a few other key problems concerning the ER Ca 2+ homeostasis have been addressed with the following conclusions: ( a) the changes induced in the ER subcompartments by receptor generation of InsP 3 vary depending on their initial [Ca 2+]. In the bulk of the system there is a rapid release whereas in the small subcompartments with low [Ca 2+] the cation is simultaneously accumulated; ( b) stimulation of Ca 2+ release by receptor-generated InsP 3 is inhibited when the lumenal level is below a threshold, suggesting a regulation by [cation 2+] er of the InsP 3 receptor activity (such a phenomenon had already been reported, however, but only in subcellular fractions analyzed in vitro); and ( c) the maintenance of a relatively constant level of cytosolic [Ca 2+], observed when the cells are incubated in Ca 2+-free medium, depends on the continuous release of the cation from the ER, with ensuing activation in the plasma membrane of the channels thereby regulated (capacitative influx). 相似文献
15.
In cardiac muscle, intracellular Ca 2+ and Mg 2+ are potent regulators of calcium release from the sarcoplasmic reticulum (SR). It is well known that the free [Ca 2+] in the SR ([Ca 2+] L) stimulates the Ca 2+ release channels (ryanodine receptor [RYR]2). However, little is known about the action of luminal Mg 2+, which has not been regarded as an important regulator of Ca 2+ release. 相似文献
16.
Recycling of vesicles of the regulated secretory pathway presumably involves passage through an early endosomal compartment as an intermediate step. To learn more about the involvement of endosomes in the recycling of synaptic and secretory vesicles we studied in vitro fusion of early endosomes derived from pheochromocytoma (PC12) cells. Fusion was not affected by cleavage of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins synaptobrevin and syntaxin 1 that operate at the exocytotic limb of the pathway. Furthermore, fusion was inhibited by the fast Ca 2+ chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetra-acetic acid but not by the slow Ca 2+ chelator EGTA. Endosome fusion was restored by the addition of Ca 2+ with an optimum at a free Ca 2+ concentration of 0.3 × 10 −6 M. Other divalent cations did not substitute for Ca 2+. A membrane-permeant EGTA derivative caused inhibition of fusion, which was reversed by addition of Ca 2+. We conclude that the fusion of early endosomes participating in the recycling of synaptic and neurosecretory vesicles is mediated by a set of SNAREs distinct from those involved in exocytosis and requires the local release of Ca 2+ from the endosomal interior. 相似文献
18.
Kinesin and myosin have been proposed to transport intracellular organelles and vesicles to the cell periphery in several cell systems. However, there has been little direct observation of the role of these motor proteins in the delivery of vesicles during regulated exocytosis in intact cells. Using a confocal microscope, we triggered local bursts of Ca 2+-regulated exocytosis by wounding the cell membrane and visualized the resulting individual exocytotic events in real time. Different temporal phases of the exocytosis burst were distinguished by their sensitivities to reagents targeting different motor proteins. The function blocking antikinesin antibody SUK4 as well as the stalk-tail fragment of kinesin heavy chain specifically inhibited a slow phase, while butanedione monoxime, a myosin ATPase inhibitor, inhibited both the slow and fast phases. The blockage of Ca 2+/calmodulin-dependent protein kinase II with autoinhibitory peptide also inhibited the slow and fast phases, consistent with disruption of a myosin-actin– dependent step of vesicle recruitment. Membrane resealing after wounding was also inhibited by these reagents. Our direct observations provide evidence that in intact living cells, kinesin and myosin motors may mediate two sequential transport steps that recruit vesicles to the release sites of Ca 2+-regulated exocytosis, although the identity of the responsible myosin isoform is not yet known. They also indicate the existence of three semistable vesicular pools along this regulated membrane trafficking pathway. In addition, our results provide in vivo evidence for the cargo-binding function of the kinesin heavy chain tail domain. 相似文献
19.
Calcium handling in pancreatic β-cells is important for intracellular signaling, the control of electrical activity, and insulin secretion. The endoplasmic reticulum (ER) is a key organelle involved in the storage and release of intracellular Ca 2+. Using mathematical modeling, we analyze the filtering properties of the ER and clarify the dual role that it plays as both a Ca 2+ source and a Ca 2+ sink. We demonstrate that recent time-dependent data on the free Ca 2+ concentration in pancreatic islets and β-cell clusters can be explained with a model that uses a passive ER that takes up Ca 2+ when the cell is depolarized and the cytosolic Ca 2+ concentration is elevated, and releases Ca 2+ when the cell is repolarized and the cytosolic Ca 2+ is at a lower concentration. We find that Ca 2+-induced Ca 2+ release is not necessary to explain the data, and indeed the model is inconsistent with the data if Ca 2+-induced Ca 2+ release is a dominating factor. Finally, we show that a three-compartment model that includes a subspace compartment between the ER and the plasma membrane provides the best agreement with the experimental Ca 2+ data. 相似文献
20.
Abundant evidences demonstrate that deuterium oxide (D 2O) modulates various secretory activities, but specific mechanisms remain unclear. Using AtT20 cells, we examined effects of D 2O on physiological processes underlying β-endorphin release. Immunofluorescent confocal microscopy demonstrated that 90% D 2O buffer increased the amount of actin filament in cell somas and decreased it in cell processes, whereas β-tubulin was not affected. Ca 2+ imaging demonstrated that high-K +-induced Ca 2+ influx was not affected during D 2O treatment, but was completely inhibited upon D 2O washout. The H 2O/D 2O replacement in internal solutions of patch electrodes reduced Ca 2+ currents evoked by depolarizing voltage steps, whereas additional extracellular H 2O/D 2O replacement recovered the currents, suggesting that D 2O gradient across plasma membrane is critical for Ca 2+ channel kinetics. Radioimmunoassay of high-K +-induced β-endorphin release demonstrated an increase during D 2O treatment and a decrease upon D 2O washout. These results demonstrate that the H 2O-to-D 2O-induced increase in β-endorphin release corresponded with the redistribution of actin, and the D 2O-to-H 2O-induced decrease in β-endorphin release corresponded with the inhibition of voltage-sensitive Ca 2+ channels. The computer modeling suggests that the differences in the zero-point vibrational energy between protonated and deuterated amino acids produce an asymmetric distribution of these amino acids upon D 2O washout and this causes the dysfunction of Ca 2+ channels. 相似文献
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