共查询到20条相似文献,搜索用时 15 毫秒
1.
P. C. Wood R. J. H. Wojcikiewicz J. Burgess† C. M. Castleden S. R. Nahorski 《Journal of neurochemistry》1994,62(6):2219-2223
Abstract: The effects of aluminium (as Al3+ ) on carbachol-induced inositol 1,4,5-trisphosphate (lnsP3 ) production arid Ca2+ mobilisation were assessed in electropermeabilised human SH-SY5Y neuroblastoma cells. Al3+ had no effect on lnsP3 -induced Ca2+ release but appreciably reduced carbachol-induced Ca2+ release (lC50 of ∼90 μ M ). Aβ3+ also inhibited lnsP3 production (lC60 of ∼15 μ M ). Dimethyl hydroxypyridin-4-one, a potent Al3+ chelator (K5 = 31), at 100 μ M was able to abort and reverse the effects of Al3+ on both Ca2+ release and lnsP3 production. These data suggest that, in permeabilised cells, the effect of Al3+ on the phosphoinositide-mediated signalling pathway is at the level of phosphatidylinositol 4,5-bisphosphate hydrolysis. This may reflect interference with receptor-G protein-phospholipase C coupling or an interaction with phosphatidylinositol 4,5-bisphosphate. 相似文献
2.
F. M. J. Heemskerk L. H. Schrama W. E. J. M. Ghijsen P. N. E. De Graan F. H. Lopes da Silva W. H. Gispen 《Journal of neurochemistry》1991,56(6):1827-1835
Abstract: Recently we have shown that 4-aminopyridine (4-AP), a drug known to enhance transmitter release, stimulates the phosphorylation of the protein kinase C substrate B-50 (GAP-43) in rat brain synaptosomes and that this effect is dependent on the presence of extracellular Ca2+ . Hence, we were interested in the relationship between changes induced by 4-AP in the intracellular free Ca2+ concentration ([Ca2+ ]i ) and B-50 phosphorylation in synaptosomes. 4-AP (100 μ M ) elevates the [Ca2+ ]i (as determined with fura-2) to approximately the same extent as depolarization with 30 m M K+ (from an initial resting level of 240 n M to ∼480 n M after treatment). However, the underlying mechanisms appear to be different: In the presence of 4-AP, depolarization with K+ still evoked an increase in [Ca2+ ]i , which was additive to the elevation caused by 4-AP. Several Ca2+ channel antagonists (CdCl2 , LaCl3 , and diphenylhydantoin) inhibited the increase in B-50 phosphorylation by 4-AP. It is interesting that the increase in [Ca2+ ]i and the increase in B-50 phosphorylation by 4-AP were attenuated by tetrodotoxin, a finding pointing to a possible involvement of Na+ channels in this action. These results suggest that 4-AP (indirectly) stimulates both Ca2+ influx and B-50 phosphorylation through voltage-dependent channels by a mechanism dependent on Na+ channel activity. 相似文献
3.
Fumi Katoh Kazuo Kitamura Hiromi Niina Ryuichi Yamamoto Hisanori Washimine †Kenji Kangawa Yoshitaka Yamamoto Hideyuki Kobayashi Tanenao Eto Akihiko Wada 《Journal of neurochemistry》1995,64(1):459-461
Abstract: In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca2+ -dependent exocytotic cosecretion of proadrenomedullin N-terminal 20 peptide (PAMP) (EC50 = 50.1 µ M ) and catecholamines (EC50 = 63.0 µ M ), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP[1–20]NH2 inhibited carbachol-induced 22 Na+ influx via nicotinic receptors (IC50 = 2.5 µ M ) in a noncompetitive manner and thereby reduced carbachol-induced 45 Ca2+ influx via voltage-dependent Ca2+ channels (IC50 = 1.0 µ M ) and catecholamine secretion (IC50 = 1.6 µ M ). It did not alter high K+ -induced 45 Ca2+ influx via voltage-dependent Ca2+ channels or veratridine-induced 22 Na+ influx via voltage-dependent Na+ channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca2+ -dependent exocytosis in response to nicotinic receptor stimulation. 相似文献
4.
Involvement of Calcium Influx in Muscarinic Cholinergic Regulation of Phospholipase C in Cerebellar Granule Cells 总被引:4,自引:0,他引:4
Abstract: Inositol phosphate accumulation on carbachol stimulation of rat cerebellar granule cells shows a marked dependence on factors affecting cytosolic Ca2+ concentration ([Ca2+ ]c ). After 5 min, potassium depolarisation caused a modest accumulation of inositol phosphates but augmented the response to carbachol by a factor of 2–3. These effects of potassium were dependent on an extracellular source of calcium and could be partially blocked by specific (nifedipine) and nonspecific (verapamil) calcium channel blockers. Measurements of [Ca2+ ]c under a range of stimulatory conditions demonstrated a close correlation between the elevation of [Ca2+ ]c and agonist-stimulated phospholipase C (PLC) activity. The maximal potentiation of carbachol-stimulated inositol phosphate accumulation was achieved using 20 m M KCl, which increased [Ca2+ ]c from ∼20 to ∼75 n M , indicating the involvement of relatively low threshold Ca2+ channels and the high sensitivity of the relevant PLC to small changes in [Ca2+ ]c . By contrast, increases in [Ca2+ ]c induced by the Ca2+ ionophore ionomycin were associated with more modest and less potent effects on agonist-stimulated PLC. These results demonstrate a cooperative interaction between a receptor/G protein-regulated PLC and voltage-stimulated elevations of [Ca2+ ]c , which may function to integrate ionotropic and metabotropic signalling mechanisms in cerebellar granule cells. 相似文献
5.
Abstract: Recent studies have demonstrated that D1-selective and D2-selective dopamine receptor agonists inhibit catecholamine secretion and Ca2+ uptake into bovine adrenal chromaffin cells by receptor subtypes that we have identified by PCR as D5, a member of the D1-like dopamine receptor subfamily, and D4, a member of the D2-like dopamine receptor subfamily. The purpose of this study was to determine whether activation of D5 or D4 receptors inhibits influx of Na+ , which could explain inhibition of secretion and Ca2+ uptake by dopamine agonists. D1-selective agonists preferentially inhibited both dimethylphenylpiperazinium- (DMPP) and veratridine-stimulated 22 Na+ influx into chromaffin cells. The D1-selective agonists chloro-APB hydrobromide (CI-APB; 100 µ M ) and SKF-38393 (100 µ M ) inhibited DMPP-stimulated Na+ uptake by 87.5 ± 2.3 and 59.7 ± 4.5%, respectively, whereas the D2-selective agonist bromocriptine (100 µ M ) inhibited Na+ uptake by only 22.9 ± 5.0%. Veratridine-stimulated Na+ uptake was inhibited 95.1 ± 3.2 and 25.7 ± 4.7% by 100 µ M CI-APB or bromocriptine, respectively. The effect of CI-APB was concentration dependent. A similar IC50 (∼18 µ M ) for inhibition of both DMPP- and veratridine-stimulated Na+ uptake was obtained. The addition of 8-bromo-cyclic AMP (1 m M ) had no effect on either DMPP- or veratridine-stimulated Na+ uptake. These observations suggest that D1-selective agonists are inhibiting secretagogue-stimulated Na+ uptake in a cyclic AMP-independent manner. 相似文献
6.
Masaru Sorimachi Yumiko Abe †Katsutoshi Furukawa ‡Norio Akaike 《Journal of neurochemistry》1995,64(3):1169-1174
Abstract: We examined the mechanism underlying the ATP-induced increase in the cytosolic Ca2+ concentration ([Ca]in ) in acutely isolated chick ciliary ganglion neurons, using fura-2 microfluorometry. The ATP-induced increase in [Ca]in was dependent on external Ca2+ , was blocked in a dose-dependent manner by reactive blue 2, and was substantially inhibited by both L- and N-type Ca2+ channel blockers. ATP was effective in increasing [Ca]in in the presence of a desensitizing concentration of nicotine (100 µ M ), and simultaneous addition of maximal doses of ATP and nicotine caused an additive increase in [Ca]in , suggesting that ATP acts on a site distinct from nicotinic acetylcholine receptors. ATP also increased the cytosolic Na+ concentration as determined by sodium-binding benzofuran isophthalate microfluorometry. These results suggest that ATP increases Na+ influx through P2 purinoceptor-associated channels resulting in membrane depolarization, which in turn increases Ca2+ influx through voltage-dependent Ca2+ channels. However, ATP still caused a small increase in [Ca]in under Na+ -free conditions, and this [Ca]in increase was little affected by Ca2+ channel blockers. ATP also increased Mn2+ influx under Na+ -free conditions, as indicated by quenching of fura-2 fluorescence. These results suggest that nonselective cationic channels activated by ATP are permeable not only to Ca2+ but also to Mn2+ , in addition to monovalent cations. 相似文献
7.
Kari R. Hoyt Sunita Rajdev Cheryl L. Fattman Ian J. Reynolds 《Journal of neurochemistry》1995,64(5):2049-2056
Abstract: We investigated the modulation of (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced increases in intracellular free Ca2+ ([Ca2+ ]i ) and intracellular free Mg2+ ([Mg2+ ]i ) by cyclothiazide and GYKI 52466 using microspectrofluorimetry in single cultured rat brain neurons. AMPA-induced changes in [Ca2+ ]i were increased by 0.3–100 µ M cyclothiazide, with an EC50 value of 2.40 µ M and a maximum potentiation of 428% of control values. [Ca2+ ]i responses to glutamate in the presence of N -methyl- d -aspartate (NMDA) receptor antagonists were also potentiated by 10 µ M cyclothiazide. The response to NMDA was not affected, demonstrating specificity of cyclothiazide for non-NMDA receptors. Almost all neurons responded with an increase in [Ca2+ ]i to both kainate and AMPA in the absence of extracellular Na+ , and these Na+ -free responses were also potentiated by cyclothiazide. GYKI 52466 inhibited responses to AMPA with an IC50 value of 12.0 µ M . Ten micromolar cyclothiazide significantly decreased the potency of GYKI 52466. However, the magnitude of this decrease in potency was not consistent with a competitive interaction between the two ligands. Cyclothiazide also potentiated AMPA- and glutamate-induced increases in [Mg2+ ]i . These results are consistent with the ability of cyclothiazide to decrease desensitization of non-NMDA glutamate receptors and may provide the basis for the increase in non-NMDA receptor-mediated excitotoxicity produced by cyclothiazide. 相似文献
8.
Abstract: Human NT2-N neurons express Ca2+ -permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPA-GluRs) and become vulnerable to excitotoxicity when AMPA-GluR desensitization is blocked with cyclothiazide. Although the initial increase in intracellular Ca2+ levels ([Ca2+ ]i ) was 1.9-fold greater in the presence than in the absence of cyclothiazide, Ca2+ entry via AMPA-GluRs in an early phase of the exposure was not necessary to elicit excitotoxicity in these neurons. Rather, subsequent necrosis was caused by a >40-fold rise in [Na+ ]i , which induced a delayed [Ca2+ ]i rise. Transfer of the neurons to a 5 m M Na+ medium after AMPA-GluR activation accelerated the delayed [Ca2+ ]i rise and intensified excitotoxicity. Low-Na+ medium-enhanced excitotoxicity was partially blocked by amiloride or dizocilpine (MK-801), and completely blocked by removal of extracellular Ca2+ , suggesting that Ca2+ entry by reverse operation of Na+ /Ca2+ exchangers and via NMDA glutamate receptors was responsible for the neuronal death after excessive Na+ loading. Our results serve to emphasize the central role of neuronal Na+ loading in AMPA-GluR-mediated excitotoxicity in human neurons. 相似文献
9.
Abstract: The effects of peroxides were investigated on the membrane potential, intracellular Na+ ([Na+ ]i ) and intracellular Ca2+ ([Ca2+ ]i ) concentrations, and basal glutamate release of synaptosomes. Both H2 O2 and the organic cumene hydroperoxide produced a slow and continuous depolarization, parallel to an increase of [Na+ ]i over an incubation period of 15 min. A steady rise of the [Ca2+ ]i due to peroxides was also observed that was external Ca2+ dependent and detected only at an inwardly directed Ca2+ gradient of the plasma membrane. These changes did not correlate with lipid peroxidation, which was elicited by cumene hydroperoxide but not by H2 O2 . Resting release of glutamate remained unchanged during the first 15 min of incubation in the presence of peroxides. These alterations may indicate early dysfunctions in the sequence of events occurring in the nerve terminals in response to oxidative stress. 相似文献
10.
Abstract: The Na+ /Ca2+ exchanger is an important element in the maintenance of calcium homeostasis in bovine chromaffin cells. The Na+ /Ca2+ exchanger from other cell types has been extensively studied, but little is known about its regulation in the cell. We have investigated the role of reversible protein phosphorylation in the activity of the Na+ /Ca2+ exchanger of these cells. Cells treated with 1 m M dibutyryl cyclic AMP (dbcAMP), 1 µ M phorbol 12,13-dibutyrate, 1 µ M okadaic acid, or 100 n M calyculin A showed lowered Na+ /Ca2+ exchange activity and prolonged cytosolic Ca2+ transients caused by depolarization. A combination of 10 n M okadaic acid and 1 µ M dbcAMP synergistically inhibited Na+ /Ca2+ exchange activity. Conversely, 50 µ M 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a protein kinase inhibitor, enhanced Na+ /Ca2+ exchange activity. Moreover, we used cyclic AMP-dependent protein kinase and calcium phospholipid-dependent protein kinase catalytic subunits to phosphorylate isolated membrane vesicles and found that the Na+ /Ca2+ exchange activity was inhibited by this treatment. These results indicate that reversible protein phosphorylation modulates the activity of the Na+ /Ca2+ exchanger and suggest that modulation of the exchanger may play a role in the regulation of secretion. 相似文献
11.
Abstract: The role of the Na+ /Ca2+ exchanger and intracellular nonmitochondrial Ca2+ pool in the regulation of cytosolic free calcium concentration ([Ca2+ ]i ) during catecholamine secretion was investigated. Catecholamine secretion and [Ca2+ ]i were simultaneously monitored in a single chromaffin cell. After high-K+ stimulation, control cells and cells in which the Na+ /Ca2+ exchange activity was inhibited showed similar rates of [Ca2+ ]i elevation. However, the recovery of [Ca2+ ]i to resting levels was slower in the inhibited cells. Inhibition of the exchanger increased the total catecholamine secretion by prolonging the secretion. Inhibition of the Ca2+ pump of the intracellular Ca2+ pool with thapsigargin caused a significant delay in the recovery of [Ca2+ ]i and greatly enhanced the secretory events. These data suggest that both the Na+ /Ca2+ exchanger and the thapsigargin-sensitive Ca2+ pool are important in the regulation of [Ca2+ ]i and, by modulating the time course of secretion, are important in determining the extent of secretion. 相似文献
12.
Goizane Marcaida Elena Kosenko María-Dolores Miñana Santiago Grisolía Vicente Felipo 《Journal of neurochemistry》1996,66(1):99-104
Abstract: In primary cultures of cerebellar neurons glutamate neurotoxicity is mainly mediated by activation of the NMDA receptor, which allows the entry of Ca2+ and Na+ into the neuron. To maintain Na+ homeostasis, the excess Na+ entering through the ion channel should be removed by Na+ ,K+ -ATPase. It is shown that incubation of primary cultured cerebellar neurons with glutamate resulted in activation of the Na+ ,K+ -ATPase. The effect was rapid, peaking between 5 and 15 min (85% activation), and was maintained for at least 2 h. Glutamate-induced activation of Na+ ,K+ -ATPase was dose dependent: It was appreciable (37%) at 0.1 µ M and peaked (85%) at 100 µ M . The increase in Na+ ,K+ -ATPase activity by glutamate was prevented by MK-801, indicating that it is mediated by activation of the NMDA receptor. Activation of the ATPase was reversed by phorbol 12-myristate 13-acetate, an activator of protein kinase C, indicating that activation of Na+ ,K+ -ATPase is due to decreased phosphorylation by protein kinase C. W-7 or cyclosporin, both inhibitors of calcineurin, prevented the activation of Na+ ,K+ -ATPase by glutamate. These results suggest that activation of NMDA receptors leads to activation of calcineurin, which dephosphorylates an amino acid residue of the Na+ ,K+ -ATPase that was previously phosphorylated by protein kinase C. This dephosphorylation leads to activation of Na+ ,K+ -ATPase. 相似文献
13.
SAXITOXIN TETRODOTOXIN AND THE METABOLISM AND CATION FLUXES IN ISOLATED CEREBRAL TISSUES 总被引:2,自引:0,他引:2
Abstract— Saxitoxin and tetrodotoxin at low concentrations (10−7 -10−8 M) exerted similar inhibitory effects on the increase in lactate production and the redistrjbution of Na+ and K+ that normally accompany electrical stimulation of rat cerebral cortical slices. In contrast, the toxins exerted dissimilar effects on the production of lactate in response to low concentrations of Ca2+ in the medium. Inhibition by tetrodotoxin occurred at a higher concentration of Ca2+ and was significantly greater than that produced by saxitoxin at concentrations of Ca2+ below 0.75 mM. These differences were not related to differential effects on the redistribution of Na+ and K+ under such conditions. The toxins had different effects on Ca2+ influx. Tetrodotoxin, but not saxitoxin, inhibited the influx of Ca2+ in the absence of electrical stimulation. The influx of Ca2+ increased when electrical pulses were applied and tetrodotoxin inhibited this increase, whereas saxitoxin potentiated influx of Ca2+ during stimulation. Our results suggest that metabolic responses to conditions that increase excitability are not governed solely by changes in the distribution of Na+ and K+ . The differential effects of the toxins on Ca2+ fluxes suggest that one site of Ca2+ entry during electrical stimulation may be functionally independent of Na+ entry. 相似文献
14.
Abstract: Increasing extracellular pH from 7.4 to 8.5 caused a dramatic increase in the time required to recover from a glutamate (3 µ M , for 15 s)-induced increase in intracellular Ca2+ concentration ([Ca2+ ]i ) in indo-1-loaded cultured cortical neurons. Recovery time in pH 7.4 HEPES-buffered saline solution (HBSS) was 126 ± 30 s, whereas recovery time was 216 ± 19 s when the pH was increased to 8.5. Removal of extracellular Ca2+ did not inhibit the prolongation of recovery caused by increasing pH. Extracellular alkalinization caused rapid intracellular alkalinization following glutamate exposure, suggesting that pH 8.5 HBSS may delay Ca2+ recovery by affecting intraneuronal Ca2+ buffering mechanisms, rather than an exclusively extracellular effect. The effect of pH 8.5 HBSS on Ca2+ recovery was similar to the effect of the mitochondrial uncoupler carbonyl cyanide p -(trifluoromethoxyphenyl)hydrazone (FCCP; 750 n M ). However, pH 8.5 HBSS did not have a quantitative effect on mitochondrial membrane potential comparable to that of FCCP in neurons loaded with a potential-sensitive fluorescent indicator, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine iodide (JC-1). We found that the effect of pH 8.5 HBSS on Ca2+ recovery was completely inhibited by the mitochondrial Na+ /Ca2+ exchange inhibitor CGP-37157 (25 µ M ). This suggests that increased mitochondrial Ca2+ efflux via the mitochondrial Na2+ /Ca2+ exchanger is responsible for the prolongation of [Ca2+ ]i recovery caused by alkaline pH following glutamate exposure. 相似文献
15.
Abstract— The rate of efflux of 45 Ca2+ from slices of rat cerebral cortex was resolved into two exponential curves which were attributed to an extracellular component and an intracellular or bound component. Electrical stimulation increased efflux of 45 Ca2+ from the more stable pool and the time course for the redistribution of Na+ and K+ paralleled that for the increased efflux of Ca2+ . This effect of stimulationwas dependent on the presence of Na+ in the incubation medium. Lack of Na+ in the medium during loading of the slices with 45 Ca2+ increased uptake but on subsequent transfer to a medium containing Na+ , electrical pulses failed to increase the rate of efflux of 45 Ca2+ . In unstimulated slices, the rate of efflux of 45 Ca2+ was dependent upon the concentration ratio of Na+ to Ca2+ in the incubation medium. Saxitoxin and tetrodotoxin inhibited the increased efflux of 45 Ca2+ that occurred during electrical stimulation but exerted no effect on Ca2+ -Ca2+ exchange. Our results suggest that there is a Na+ -dependent turnover of Ca2+ in brain slices which may involve changes in affinity at a common binding site. The possible involvement of such a Na+ -Ca2+ interaction in the regulation of neurotransmitter function is discussed. 相似文献
16.
Walter E. Riedell 《Physiologia plantarum》1987,69(2):299-304
When 1 m M spermidine or spermine was included in an absorption solution which contained 20 m M Na+ and 1 m M Rb+ , Na+ influx into excised maize roots ( Zea mays L. cv. Golden Cross Bantam) was reduced. Rb+ influx was reduced in the presence of spermidine and uneffected in the presence of spermine when compared with control solutions. When 1 m M Ca2+ replaced the polyamines, Na+ influx was strongly reduced and Rb+ influx was promoted. Rb+ influx from 1 m M Rb+ solutions which did not contain Na+ was also promoted by 1 m M Ca2+ , but was inhibited by 1 m M spermidine. This Ca2+ promotion of Rb+ influx could be reversed by 10 times greater concentration of spermidine in the absorption solution. H+ efflux from excised roots was inhibited by spermidine when compared with Ca2+ or control solutions, however, the plasma membrane ATPase was not inhibited by spermidine. It is concluded that external Ca2+ plays two separate roles in membrane function, only one of which can be substituted for by polyamines. The first role, maintenance of membrane integrity, can be substituted for by spermidine or spermine. The second function, maintenance of the Rb+ transport mechanism, is Ca2+ specific and cannot be substituted for by spermidine or spermine. The results of this study are discussed in terms of electrostatic interactions between the plasma membrane and the Ca2+ or polyamines. 相似文献
17.
Shei-Ying Hu Shu-Ling Song Mei-Ying Ho Sheau-Huei Chueh 《Journal of neurochemistry》1997,68(2):846-854
Abstract: Prior treatment of NG108-15 cells with phosphatase inhibitors including okadaic acid and calyculin A inhibited the elevation of cytosolic Ca2+ concentration ([Ca2+ ]i ) induced by bradykinin by ∼63%. This inhibition was dependent on the concentration of okadaic acid with an IC50 of 0.15 n M . Okadaic acid treatment only lowered the maximal response of [Ca2+ ]i increase and had no effect on the EC50 value for bradykinin regardless of the presence of extracellular Ca2+ . Neither the capacity of 45 Ca2+ accumulation within intracellular nonmitochondrial Ca2+ stores nor the magnitude of [Ca2+ ]i increase induced by thapsigargin was reduced by the treatment of okadaic acid. In contrast, the same phosphatase inhibitor treatment inhibited the bradykinin-evoked inositol 1,4,5-trisphosphate (IP3 ) generation, the Mn2+ influx, and the capacity of mitochondrial Ca2+ accumulation. Furthermore, the sensitivity of IP3 in the Ca2+ release was suppressed by okadaic acid pretreatment. Our results suggest that the reduction of bradykinin-induced [Ca2+ ]i rise by the promotion of protein phosphorylation was attributed to the reduced activity of phospholipase C, the decreased sensitivity to IP3 , and the slowed rate of Ca2+ influx. Thus, phosphorylation plays a role in bradykinin-sensitive Ca2+ signaling cascade in NG108-15 cells. 相似文献
18.
Modulation of Ion Gradients and Glutamate Release in Cultured Cerebellar Granule Cells by Ouabain 总被引:8,自引:0,他引:8
Abstract: Upon addition of the cardiac glycoside ouabain to cultured cerebellar granule cells, an immediate increase in intracellular free sodium is evoked mediated by two pathways, a voltage-sensitive channel blocked by tetrodotoxin and a channel sensitive to flunarizine. Ouabain induces a steady plasma membrane depolarization in low Ca2+ medium; whereas in the presence of Ca2+ , a distinct discontinuity is observed always preceded by a large increase in intracellular free Ca2+ ([Ca2+ ]c ). The plateau component of the increase can be inhibited additively by the L-type Ca2+ channel antagonist nifedipine, the spider toxin Aga-Gl, and the NMDA receptor antagonist MK-801. Single-cell imaging reveals that the [Ca2+ ]c increase occurs asynchronously in the cell population and is not dependent on a critical level of extracellular glutamate or synaptic transmission between the cells. A prolonged release of glutamate is also observed that is predominantly Ca2+ dependent for the first 6–10 min after the evoked increase in [Ca2+ ]c . This release is four times as large as that observed with 50 m M KCl and is predominantly exocytotic because release was inhibited by tetanus toxin, the V-type ATPase inhibitor bafilomycin, and Aga-Gl. It is proposed, therefore, that ouabain induces a period of membrane excitability culminating in a sustained exocytosis above that observed upon permanent depolarization with KCl. 相似文献
19.
Low-K+ , high-Na+ cells of strain RL21a of Neurospora crassa , in steady state with 25 m M Na+ , were used to study K+ /Na+ exchanges in the presence or absence of Ca2+ and Mg2+ . In the presence of Ca2+ and Mg2+ , a low concentration of K+ (0.3 m M ) triggered a rapid exchange, but in the absence of the divalents, a high K+ concentration (30 m M ) was required to initiate the exchange at a rapid rate. In the absence of Ca2+ and Mg2+ , K+ uptake did not occur at low K+ concentration, internal K+ did not regulate Na+ influx in the presence of external K+ , and the efflux of Na+ proceeded at maximum activity at very low-K+ contents. 相似文献
20.
Extracellular Calcium Has Distinct Effects on Fast and Slow Components of the Depolarization-Induced Secretory Response from Chromaffin Cells 总被引:1,自引:0,他引:1
R. Granja V. Izaguirre S. Calvo C. González-García V. Ceña 《Journal of neurochemistry》1996,67(3):1056-1062
Abstract: An increase in extracellular Ca2+ concentration from 0.25 to 10 m M enhanced secretion of norepinephrine and epinephrine induced by a high extracellular K+ concentration (75 m M ). The increment in extracellular Ca2+ concentration also increased the observed peak inward Ca2+ current in response to long (10-s) depolarizing pulses from a holding potential of −55 mV to +5 mV, from about −26 to −400 pA. However, the total amount of Ca2+ influx into the cell only increased when the extracellular Ca2+ concentration was raised from 0.25 to 1 m M and then remained constant up to 10 m M extracellular Ca2+ . ATP is cosecreted with catecholamines following a depolarizing stimulus. Kinetic studies indicated that ATP secretion had two components with time constants, in the presence of 2.5 m M extracellular Ca2+ , of ∼4 and 41 s, being the fast component of secretion produced by the exocytosis of ∼220 chromaffin granules. The results suggest that, for a given depolarizing stimulus, the size and rate of release for the fast and slow components of secretion are dependent on extracellular Ca2+ concentration. 相似文献