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61.
Hiroko Matsuda 《Pflügers Archiv : European journal of physiology》1986,407(5):465-475
An inward current characterized by a slow inactivation, was induced when the extracellular Ca2– concentration was reduced by EGTA. It was suppressed by replacing external Na– with Tris+ or by D-600, increased by epinephrine, and was not affected by TTX. These findings suggest that this current is carried by Na+ ions through the Ca channels. The Na current decreased in amplitude as the concentration of external divalent cations was elevated. Blocking the Na current by divalent cations could be approximated by a bimolecular interaction between divalent cation and channel, with a dissociation constant of 1.2 M for Ca2+ and 60 M for Mg2+. Single channel currents were recorded in the cell-attached configuration. With a pipette solution of pCa=7.5 or pCa>8, the single channel I-V relationship was linear and the slope conductance was 70–75 pS. For 40 mV depolarizations from the resting potential, unitary currents were smaller at pCa=6 than at pCa=7.5. However, single channel events, which were observed after the repolarizing step to the resting potential, were much the same amplitude. The open time histogram was fitted with a single exponential having a time constant of 1.9 ms at around –40 mV (pCa>8, with 5 M Bay K 8644 in the bath solution), which was decreased with increasing the Ca2+ concentration in the pipette solution. Noise power spectra of patch currents at pCa=6 revealed a high-frequency component at around 1500 Hz. These results suggest that Ca binding to the sites with a high affinity for Ca2+ blocks the Na conductance in Ca channels. Reduction of the unitary current at higher concentrations of Ca2+ might be attributed to a rapid block by Ca2+. 相似文献
62.
为了探讨趋化性细胞因子在体外对人Tc1和Tc2亚群细胞内Ca2 + 浓度变化的影响 ,从PBMC中分离纯化CD8+ T细胞 ,在特定细胞因子及细胞因子抗体作用下 ,体外定向诱导出能长期培养的Tc1和Tc2细胞系 ,用免疫荧光染色结合流式细胞术分析对其进行鉴定后 ,通过流式细胞术检测在趋化性细胞因子刺激前后 ,细胞内Ca2 + 浓度的变化。发现受SDF 1作用后 ,Tc1及Tc2细胞内Ca2 + 浓度变化均不明显 ,而IP 10刺激后 ,Tc1及Tc2细胞内Ca2 + 水平在短时间内明显上调 ,且在Tc1胞内的上升幅度远高于Tc2细胞 ,在MIP 1β刺激后 ,也观察到类似趋势 ;受Eotaxin刺激后 ,Tc1及Tc2细胞内Ca2 + 水平均有微小上升 ,在Tc2细胞内的上升幅度略高于Tc1细胞。说明Tc1和Tc2细胞受趋化性细胞因子作用后 ,细胞内Ca2 + 浓度有不同程度的变化 ,且与趋化性细胞因子受体的表达呈现一定的相关性。 相似文献
63.
Voltage gated ion channels on the somatic membrane of rat cerebellar Purkinje cells were studied in dissociated cell culture with the combination of cell-attached and whole-cell variation of patch clamp technique. The method enables us to record local somatic membrane current under an improved space clamp condition. Transient (fast-inactivating) and steady (slow inactivating) Ca channel currents, Na current, transient (fast-inactivating) and steady (slow-inactivating) K currents, were observed. Transient and steady Ca channel currents were activated at test potentials more positive than –40 mV and –20 mV, respectively (in 50 mM external Ba). The transient current inactivated with a half-decay time of 10–30 ms during maintained depolarizing pulses, while the steady current showed relatively little inactivation. Na current was activated at more positive potentials than –60 mV, and inactivated with a half-decay time of less than 5 ms. Transient and steady K outward currents were recorded at more positive potential than –20 mV and –40 mV, respectively. The transient current inactivated with a half-decay time of 2–8 ms. Ca, Na and K channels showed different patterns of distribution on the somatic membrane. Steady Ca channels tended to cluster compared with Na or K channels. 相似文献
64.
The pro-inflammatory cytokine interleukin-1β (IL-1β) is released by cells during injury and stress, and increased neuronal expression of IL-1β is a feature of age-related neurodegeneration. We have recently reported that IL-1β has a biphasic effect on the K+-induced rise in intracellular Ca2+ concentration ([Ca2+]i) in cortical synaptosomes, exerting an inhibitory effect on the K+-induced rise in [Ca2+]i at lower (3.5 ng/mL) concentrations and a stimulatory effect on the K+-induced rise in [Ca2+]i at higher (100 ng/mL) concentrations. In the present study, we observed that the K+-induced rise in [Ca2+]i was inhibited to a similar extent by the lower concentration of IL-1β in cortical synaptosomes prepared from young (3-month-old), middle-aged (12-month-old) and aged (24-month-old) rats. In contrast, cortical synaptosomes prepared from the aged rats exhibited an increased susceptibility to the higher concentration of IL-1β, resulting in a marked elevation in [Ca2+]i. We propose that the age-related increase in neuronal concentration of IL-1β promotes a dramatic elevation in [Ca2+]i following membrane depolarization, thereby altering Ca2+ homeostasis and exacerbating neuronal vulnerability to excitotoxicity. 相似文献
65.
Effects of ruthenium red on membrane ionic currents in urinary bladder smooth muscle cells of the guinea-pig 总被引:2,自引:0,他引:2
Masaru Hirano Y. Imaizumi Katsuhiko Muraki A. Yamada Minoru Watanabe 《Pflügers Archiv : European journal of physiology》1998,435(5):645-653
Three major ionic currents, Ca2+-dependent K+ current (I
K-Ca), delayed rectifier type K+ current (I
kd) and Ca2+ current (I
Ca), were activated by depolarization under whole-cell clamp in single smooth muscle cells isolated from guinea-pig urinary
bladder. Externally applied ruthenium red (RuR) reduced the amplitude of I
K-Ca and I
Ca at 0 mV (IC50 values were 4.2 and 5.6 μM, respectively), but did not affect I
Kd. Spontaneous transient outward currents (STOCs) and caffeine-induced outward currents (I
caf) at –30 mV were reduced by external 10 μM RuR. When 10 μM RuR was added to the pipette solution, I
K-Ca during depolarization, STOCs and I
caf significantly decreased with time. RuR did not change the unitary current amplitude of the large-conductance Ca2+-dependent K+ (BK) channels, but reduced the open probability of the channel under excised patch-clamp recording mode. RuR reduced the
channel activity more effectively from the cytosolic face than from the other. This inhibition decreased when the cytosolic
Ca2+ concentration was increased. These results indicate that RuR blocks BK and Ca2+ channels in urinary bladder smooth muscle cells. The decrease in I
K-Ca, STOCs and I
caf by RuR is attributable to the direct inhibition of BK channel activity, probably in addition to the inhibition of Ca2+ release from storage sites. The direct inhibition of BK channel activity by RuR may be related to the interaction of RuR
with the Ca2+-binding sites of the channel protein.
Received: 15 October 1997 / Received after revision and accepted: 25 November 1997 相似文献
66.
Effect of stretch on calcium channel currents recorded from the antral circular myocytes of guinea-pig stomach 总被引:7,自引:0,他引:7
Wen Xie Xu Sung Joon Kim Sang Jeong Kim Insuk So Tong Mook Kang Jong Chul Rhee Ki Whan Kim 《Pflügers Archiv : European journal of physiology》1996,432(2):159-164
The effect of membrane stretch on voltage-activated Ba2+ current (I
Ba) was studied in antral circular myocytes of guinea-pig using the whole- cell patch-clamp technique. The changes in cell volume
were elicited by superfusing the myocytes with anisosmotic solutions. Hyposmotic superfusate (202 mosmol/l) induced cell swelling
and increased peak values of I
Ba at 0 mV (from −406.6 ± 45.5 pA to −547.5 ± 65.6 pA, mean ± SEM, n = 8) and hyperosmotic superfusate (350 mosmol/l) induced cell shrinkage and decreased peak values of I
Ba at 0 mV (to −269.5 ± 39.1 pA, n = 8). Such changes were reversible and the extent of change was dependent on the osmolarity of superfusate. The values of
normalized I
Ba at 0 mV were 1.43 ± 0.04, 1.30 ± 0.06, 1.23 ± 0.04, 1.19 ± 0.04, 1 and 0.68 ± 0.06 at 202, 220, 245, 267, 290 and 350 mosmol/l,
respectively (n = 8). I
Ba was almost completely blocked by nicardipine (5 μM) under hyposmotic conditions. The values of steady-state half-inactivation
voltage (−37.7 ± 3.3 and −36.5 ± 2.6 mV, under control and hyposmotic conditions, respectively) or the half-activation voltage
(−13.6 ± 2.3 and −13.9 ± 1.9 mV) of I
Ba were not significantly changed (P > 0.05, n = 6). Cell membrane capacitance was slightly increased from 50.00 ± 2.86 pF to 50.22 ± 2.82 pF by a hyposmotic superfusate
(P < 0.05, n = 6). It is suggested that cell swelling increases voltage-operated L-type calcium channel current and that such a property
is related to the response of gastric smooth muscle to mechanical stimuli.
Received: 14 November 1995/Received after revision and accepted: 8 January 1996 相似文献
67.
Jyoti V. Chauthaiwale Takayuki Sakai Samuel E. Taylor Indu S. Ambudkar 《Pflügers Archiv : European journal of physiology》1996,432(1):105-111
The molecular mechanism(s) involved in mediating Ca2+ entry into rat parotid acinar and other non-excitable cells is not known. In this study we have examined the kinetics of
Ca2+ entry in fura-2-loaded parotid acinar cells, which were treated with thapsigargin to deplete internal Ca2+ pools (Ca2+-pool-depleted cells). The rate of Ca2+ entry was determined by measuring the initial increase in free cytosolic [Ca2+] ([Ca2+]i) in Ca2+-pool-depleted, and control (untreated), cells upon addition of various [Ca2+] to the medium. In untreated cells, a low-affinity component was detected with K
Ca = 3.4 ± 0.7 mM (where K
Ca denotes affinity for Ca2+) and V
max = 9.8 ± 0.4 nM [Ca2+]i /s. In thapsigargin-treated cells, two Ca2+ influx components were detected with K
Ca values of 152 ± 79 μM (V
max = 5.1 ± 1.9 nM [Ca2+]i/s) and 2.4 ± 0.9 mM (V
max = 37.6 ± 13.6 nM [Ca2+]i/s), respectively. We have also examined the effect of Ca2+ and depolarization on these two putative Ca2+ influx components. When cells were treated with thapsigargin in a Ca2+-free medium, Ca2+ influx was higher than into cells treated in a Ca2+-containing medium and, while there was a 46% increase in the V
max of the low-affinity component (no change in K
Ca), the high-affinity component was not clearly detected. In depolarized Ca2+-pool-depleted cells (with 50 mM KCl in the medium) the high-affinity component was considerably decreased while there was
an apparent increase in the K
Ca of the low-affinity component, without any change in the V
max. These results demonstrate that Ca2+ influx into parotid acinar cells (1) is increased (four- to five-fold) upon internal Ca2+ pool depletion, and (2) is mediated via at least two components, with low and high affinities for Ca2+.
Received: 30 October 1995/Received after revisionand accepted: 13 December 1995 相似文献
68.
Luis Gandía Baldomero Lara Julita S. Imperial Mercedes Villarroya Almudena Albillos Rosario Maroto A. G. García Baldomero M. Olivera 《Pflügers Archiv : European journal of physiology》1997,435(1):55-64
The characteristics of the binding sites for the Conus magus toxins ω-conotoxin MVIIC and ω-conotoxin MVIID, as well as their effects on K+-evoked 45Ca2+ entry and whole-cell Ba2+ currents (I
Ba), and K+-evoked catecholamine secretion have been studied in bovine adrenal chromaffin cells. Binding of [125I] ω-conotoxin GVIA to bovine adrenal medullary membranes was displaced by ω-conotoxins GVIA, MVIIC and MVIID with IC50 values of around 0.1, 4 and 100 nM, respectively. The reverse was true for the binding of [125I] ω-conotoxin MVIIC, which was displaced by ω-conotoxins MVIIC, MVIID and GVIA with IC50 values of around 30, 80 and 1.200 nM, respectively. The sites recognized by ω-conotoxins MVIIC and MVIID in bovine brain
exhibited higher affinities (IC50 values of around 1 nM). Both ω-conotoxin MVIIC and MVIID blocked I
Ba by 70–80%; the higher the [Ba2+]o of the extracellular solution the lower the blockade induced by ω-conotoxin MVIIC. This was not the case for ω-conotoxin
MVIID; high Ba2+ (10 mM) slowed down the development of blockade but the maximum blockade achieved was similar to that obtained in 2 mM Ba2+. A further difference between the two toxins concerns their reversibility; washout of ω-conotoxin MVIIC did not reverse the
blockade of I
Ba while in the case of ω-conotoxin MVIID a partial, quick recovery of current was produced. This component was irreversibly
blocked by ω-conotoxin GVIA, suggesting that it is associated with N-type Ca2+ channels. Blockade of K+-evoked 45Ca2+ entry produced results which paralleled those obtained by measuring I
Ba. Thus, 1 μM of each of ω-conotoxin GVIA and MVIIA inhibited Ca2+ uptake by 25%, while 1 μM of each of ω-conotoxin MVIIC and MVIID caused a 70% blockade. K+-evoked catecholamine secretory responses were not reduced by ω-conotoxin GVIA (1 μM). In contrast, at 1 μM both ω-conotoxin
MVIIC and MVIID reduced the exocytotic response by 70%. These data strengthen the previously established conclusion that Q-type
Ca2+ channels that contribute to the regulation of secretion and are sensitive to ω-conotoxins MVIIC and MVIID are present in
bovine chromaffin cells. These channels, however, seem to possess binding sites for ω-conotoxins MVIIC and MVIID whose characteristics
differ considerably from those described to occur in the brain; they might represent a subset of Q-type Ca2+ channels or an entirely new subtype of voltage-dependent high-threshold Ca2+ channel.
Received: 16 April 1997 / Received after revision: 10 July 1997 / Accepted: 23 July 1997 相似文献
69.
Armando A. Lagrutta Ke-Zhong Shen André Rivard R. Alan North J. P. Adelman 《Pflügers Archiv : European journal of physiology》1998,435(5):731-739
Structural determinants of permeation in large unit conductance calcium-activated potassium channels (BK channels) were investigated.
Y293 and F294 in the P-region of dSlo were substituted by tryptophans. Compared to wild-type channels, Y293W channels displayed reduced inward unitary currents
while F294W channels exhibited normal inward current amplitudes but flickery kinetics. Both mutations produced changes in
current/voltage relations under bi-ionic conditions. Sensitivity to block by external tetraethylammonium (TEA) was affected
in both channels, and the voltage dependence of TEA block was increased in F294W channels. Both mutations also affected gating
by shifting the half-maximal activation voltage of macroscopic conductance/voltage relations to more positive potentials,
and eliminating a slow component of deactivation. The double mutant did not produce ionic currents. These data are consistent
with a model in which Y293 contributes to a potassium-binding site close to the outer mouth of the dSlo pore, while F294 contributes to an energy barrier near this site.
Received: 16 September 1997 / Received after revision: 20 November 1997 / Accepted: 21 November 1997 相似文献
70.
Bernhard F. X. Reber Benno Schindelholz 《Pflügers Archiv : European journal of physiology》1996,432(5):893-903
Bradykinin and caffeine were used as two different agonists to study inositol 1,4,5-trisphosphate (IP3)-sensitive and caffeine/ryanodine-sensitive intracellular Ca2+ release in the outgrowing neurites of nerve-growth-factor (NGF)-treated rat phaeochromocytoma cells (PC12). Changes in neuritic
intracellular free Ca2+ ([Ca2+]i) in single cells were measured after loading with a 1:1 mixture of the acetoxymethyl (AM) ester of the Ca2+-sensitive dyes Fura-red and Fluo-3, in combination with confocal microscopy. Bradykinin-induced Ca2+ release was blocked by U73211, a specific phospholipase C inhibitor. Caffeine-induced Ca2+ release was very low in neurites at rest. It increased after the cells were preloaded with Ca2+. The Ca2+ signal evoked at high concentrations of bradykinin (>500 nM) arose from a trigger zone in the proximal part of the neurite,
as a bi-directional wave towards the growth cone and cell body. The speed of neuritic Ca2+ waves was reduced in cells loaded with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-tetraacetic acid/AM. Preloading of Ca2+ stores led to increased bradykinin-induced Ca2+ release, as seen for caffeine, and faster Ca2+ wave speeds. Caffeine evoked a simultaneous [Ca2+]i rise along the neurites of Ca2+ preloaded cells. Higher Ca2+ signal amplitudes and faster Ca2+ wave speeds, but no longer-lasting IP3-induced [Ca2+]i signals, correlated with increased caffeine-induced Ca2+ release in the neurites. At low concentrations of bradykinin (<1.0 nM), the Ca2+ signals ceased to propagate as complete Ca2+ waves. Instead, repetitive stochastic Ca2+ release events (neuritic Ca2+ puffs) were observed. Neuritic Ca2+ puffs spread across only a few microns, at a slower speed than neuritic Ca2+ waves. These Ca2+ puffs represent elementary Ca2+ release units, whereby the released Ca2+ ions form these elementary events into the shape of a Ca2+ wave.
Received: 16 April 1996 / Received after revision and accepted: 13 May 1996 相似文献