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61.
Abstract: Somatostatin (SS) is a neuropeptide that is distributed in various regions of the CNS, where it may act as a neurotransmitter or neuromodulator. SS produces multiple effects in the CNS through interactions with membrane receptors. In particular, SS inhibits various secretory responses in different cell types. In the present study, we have investigated the effects of exogenous application of SS on the intracellular free Ca2+ concentration ([Ca2+ ]i ) in PC12 cells, a rat pheochromocytoma cell line. SS did reduce the magnitude of the secondary, maintained Ca2+ influx brought about by K+ depolarization. Similar effects were obtained with the application of SS analogues, such as d -Trp8 -SS, d -Trp8 - d -Cys14 -SS, CGP-23996, and SMS-201995. In addition, treatment with cyclo-SS, a SS antagonist, did not alter [Ca2+ ]i . Experiments with selective blockers of different voltage-dependent Ca2+ channels, such as methoxyverapamil (D600) and Ω-conotoxin GVIA, demonstrated that the effects of SS on [Ca2+ ]i were mediated by voltage-dependent Ca2+ channels of the L type. Control experiments with a membrane potential indicator, i.e., the fluorescent dye bisoxonol, excluded that SS influenced the level of the membrane potential. SS effects on PC12 cells suggest the possibility that this neuropeptide plays a role in the modulation of cell functional activity by altering Ca2+ influx. 相似文献
62.
Abstract: The role of voltage-sensitive Ca2+ channels in mediating Ca2+ influx during ischemia was investigated in NG108-15 cells, a neuronal cell line that does not express glutamate-sensitive receptor-mediated Ca2+ channels. Concurrent 31P/19F and 23Na double-quantum filtered (DQF) NMR spectra were used to monitor cellular energy status, intracellular [Ca2+] ([Ca2+]i), and intracellular Na+ content in cells loaded with the calcium indicator 1,2-bis-(2-amino-5-fluorophenoxy)ethane-N,N,N′,N′-tetraacetic acid (5FBAPTA) during ischemia and reperfusion. Cells loaded with 5FBAPTA were indistinguishable from unloaded cells except for small immediate decreases in levels of phosphocreatine (PCr) and ATP. Ischemia induced a steady decrease in intracellular pH and PCr and ATP levels, and a steady increase in intracellular Na+ content; however, a substantial increase in [Ca2+]i (about threefold) was seen only following marked impairment of cellular energy status, when PCr was undetectable and ATP content was reduced to 55% of control levels. A depolarization-induced increase in [Ca2+]i could be completely blocked by 1 µM nifedipine, whereas up to 20 µM nifedipine had no effect on the increase in [Ca2+]i seen during ischemia. These data demonstrate that voltage-gated Ca2+ channels do not mediate significant Ca2+ flux during ischemia in this cell line and suggest an important role for Ca2+i stores, the Na+/Ca2+ antiporter, or other processes linked to cellular energy status in the increase in cytosolic Ca2+ level during ischemia. 相似文献
63.
T. Ishikawa 《The Journal of membrane biology》1996,153(2):147-159
A Ca2+-activated Cl− conductance in rat submandibular acinar cells was identified and characterized using whole-cell patch-clamp technique. When
the cells were dialyzed with Cs-glutamate-rich pipette solutions containing 2 mm ATP and 1 μm free Ca2+ and bathed in N-methyl-d-glucamine chloride (NMDG-Cl) or Choline-Cl-rich solutions, they mainly exhibited slowly activating currents. Dialysis of
the cells with pipette solutions containing 300 nm or less than 1 nm free Ca2+ strongly reduced the Cl− currents, indicating the currents were Ca2+-dependent. Relaxation analysis of the ``on' currents of slowly activating currents suggested that the channels were voltage-dependent.
The anion permeability sequence of the Cl− channels was: NO−
3 (2.00) > I− (1.85) ≥ Br− (1.69) > Cl− (1.00) > bicarbonate (0.77) ≥ acetate (0.70) > propionate (0.41) ≫ glutamate (0.09). When the ATP concentration in the pipette
solutions was increased from 0 to 10 mm, the Ca2+-dependency of the Cl− current amplitude shifted to lower free Ca2+ concentrations by about two orders of magnitude. Cells dialyzed with a pipette solution (pCa = 6) containing ATP-γS (2 mm) exhibited currents of similar magnitude to those observed with the solution containing ATP (2 mm). The addition of the calmodulin inhibitors trifluoperazine (100 μm) or calmidazolium (25 μm) to the bath solution and the inclusion of KN-62 (1 μm), a specific inhibitor of calmodulin kinase, or staurosporin (10 nm), an inhibitor of protein kinase C to the pipette solution had little, if any, effect on the Ca2+-activated Cl− currents. This suggests that Ca2+/Calmodulin or calmodulin kinase II and protein kinase C are not involved in Ca2+-activated Cl− currents. The outward Cl− currents at +69 mV were inhibited by NPPB (100 μm), IAA-94 (100 μm), DIDS (0.03–1 mm), 9-AC (300 μm and 1 mm) and DPC (1 mm), whereas the inward currents at −101 mV were not. These results demonstrate the presence of a bicarbonate- and weak acid-permeable
Cl− conductance controlled by cytosolic Ca2+ and ATP levels in rat submandibular acinar cells.
Received: 9 January 1996/Revised: 20 May 1996 相似文献
64.
The mechanosensitive properties of large-conductance Ca2+-activated K+ (BK) channels from embryonic rat neuroepithelium were investigated with the cell-attached and inside-out configurations of
the patch-clamp technique. The channels were activated in both recording configurations by negative pressures applied to the
patch electrode, but reversal of the effect was total and immediate in inside-out patches whereas it was incomplete and delayed
in on-cell patches. This mechanosensitivity was not mediated by Ca2+ ions or fatty acids, suggesting that it is an intrinsic property of these channels. Cytochalasin B did not affect mechanosensitivity
in on-cell patches but increased it in inside-out patches. Kinetic studies showed that stretch increased the mean open time
of the channels and decreased the slowest time constant of their closed-time distributions. The present as well as previous
results suggest complex interactions between embryonic BK channels and their membranous and submembranous environment.
Received: 1 February 1996/Revised: 25 March 1996 相似文献
65.
66.
High-conductance calcium-activated potassium channels; Structure,pharmacology, and function 总被引:19,自引:0,他引:19
Gregory J. Kaczorowski Hans -Günther Knaus Reid J. Leonard Owen B. McManus Maria L. Garcia 《Journal of bioenergetics and biomembranes》1996,28(3):255-267
High-conductance calcium-activated potassium (maxi-K) channels comprise a specialized family of K+ channels. They are unique in their dual requirement for depolarization and Ca2+ binding for transition to the open, or conducting, state. Ion conduction through maxi-K channels is blocked by a family of venom-derived peptides, such as charybdotoxin and iberiotoxin. These peptides have been used to study function and structure of maxi-K channels, to identify novel channel modulators, and to follow the purification of functional maxi-K channels from smooth muscle. The channel consists of two dissimilar subunits, and . The subunit is a member of theslo Ca2+-activated K+ channel gene family and forms the ion conduction pore. The subunit is a structurally unique, membrane-spanning protein that contributes to channel gating and pharmacology. Potent, selective maxi-K channel effectors (both agonists and blockers) of low molecular weight have been identified from natural product sources. These agents, together with peptidyl inhibitors and site-directed antibodies raised against and subunit sequences, can be used to anatomically map maxi-K channel expression, and to study the physiologic role of maxi-K channels in various tissues. One goal of such investigations is to determine whether maxi-K channels represent novel therapeutic targets. 相似文献
67.
Ronghua Zhuge Siben Li Ter-Hsin Chen Walter H. Hsu 《Molecular reproduction and development》1995,41(1):20-28
This study investigated the underlying mechanisms of oxytocin (OT)-induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in acutely dispersed myometrial cells from prepartum sows. A dosedependent increase in [Ca2+]i was induced by OT (0.1 nM to 1 μM) in the presence and absence of extracellular Ca2+ ([Ca2+]e). [Ca2+]i was elevated by OT in a biphasic pattern, with a spike followed by a sustained plateau in the presence of [Ca2+]e. However, in the absence of [Ca2+]e, the [Ca2+]i response to OT became monophasic with a lower amplitude and no plateau, and this monophasic increase was abolished by pretreatment with ionomycin, a Ca2+ ionophore. Administration of OT (1 μM) for 15 sec increased inositol 1,4,5-trisphosphate (IP3) formation by 61%. Pretreatment with pertussis toxin (PTX, 1 μg/ml) for 2 hr failed to alter the OT-induced increase in [Ca2+]i and IP3 formation. U-73122 (30 nM to 3 μM), a phospholipase C (PLC) inhibitor, depressed the rise in [Ca2+]i by OT dose dependently. U-73122 (3 μM) also abolished the OT-induced IP3 formation. Thapsigargin (2 μM), an inhibitor of Ca2+-ATPase in the endoplasmic reticulum, did not increase [Ca2+]i. However, it did time-dependently inhibit the OT-induced increase in [Ca2+]i. Nimodipine (1 μM), a Voltage-dependent Ca2+ channel (VDCC) blocker, inhibited the OT-induced plateau by 26%. La3+ (1 μM), a nonspecific Ca2+ channel blocker, abrogated the OT-induced plateau. In whole-cell patch-clamp studies used to evaluate VDCC activities, OT (0.1 μM) increased Ca2+ Current (Ica) by 40% with no apparent changes in the current-voltage relationship. The OT-induced increase in Ica reached the maximum in 5 min, and the increase was abolished by nimodipine (1 μM). These results suggested that (1) activation of OT receptors in porcine myometrium evokes a cascade in the PTX-insensitive G-protein–PLC-IP3 signal transduction, resulting in an increase in [Ca2+]i; (2) the OT-induced increase in [Ca2+]i is characterized by a biphasic pattern, in which the spike is predominately contributed by the intracellular Ca2+ release from the IP3-sensitive pool, and to a lesser extent by Ca2+ influx, whereas the plateau is from increased Ca2+ influx; and (3) the influx is via VDCC and receptor-operated Ca2+ channels. © 1995 Wiley-Liss, Inc. 相似文献
68.
The temperature dependence of high voltage activated Ca2+ channels has been investigated in cultured dorsal root ganglion neurones from chick embryos, using the cell-attached patch-clamp technique. The dihydropyridine sensitive L-type Ca2+ channel had a conductance of 23 pS, with 110 mM Ba2+ as charge carrier and in the presence of 3 M Bay K 8644. When the temperature was raised from 15 to 30 °C, the unitary channel current amplitude increased, with Q10 value equal to 1.4. The rising phase of the averaged single-channel current became faster, with Q10 value 2.7, whereas the decay phase showed a lower temperature sensitivity. Channel open probability decreased according to an exponential distribution of open and closed times. A second type of Ca2+ channel was identified, which was DHP-insensitive and had a lower conductance with a mean value equal to 13 pS. For the current amplitude, the Q10 value was 1.3. Both activation and inactivation kinetics were strongly accelerated by an increase in temperature. The corresponding time constants gave Q10 values equal to 5.9 for activation, and 2.0 for inactivation. Peak channel open probability was highly sensitive to a change in temperature, with a Q10 value of 1.6. Finally, in -conotoxin GVIA pre-treated neurones, a non-inactivating DHP-insensitive Ca2+ channel with the lowest unitary conductance (10 pS) and a much lower temperature dependence was recorded. Single-channel current was increased by heating, with Q10 value 1.3, whereas the channel kinetics were almost unaffected by temperature. Our data are consistent with the assumption that the different temperature dependence of the Ca2+ channel behaviours may be explained by separate gating processes of three types of Ca2+ channels. 相似文献
69.
S. M. Thoroed K. Fugelli 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1994,164(1):1-10
Erythrocytes from the marine fish species ballan wrasse (Labrus berggylta Ascanius), bullhead (Myoxocephalus scorpius L.), cod (Gadus morhua L.), dab (Limanda limanda L.), eelpout (Zoarces viviparus L.), flounder (Platichthys flesus L.), lumpfish (Cyclopterus lumpus L.), plaice (Pleuronectes platessa L.), sole (Solea solea L.) and turbot (Scophthalmus maxima L.) possess the capacity for regulatory volume decrease. This property was demonstrated in vitro by reduction of the osmolality of the incubation medium from 330 to 255 mosmol·kg-1. During the 4-h incubation period only the lumpfish cells completely regained the original volume. Twenty-seven free amino compounds were present in detectable amounts in the erythrocytes. At normal osmolality the taurine content was between 14.0 mol·g dry weight-1 (lumpfish) and 147.4 mol·g dry weight-1 (sole). Except in the bullhead, taurine was the quantitatively dominating amino compound in the erythrocytes from all species, and accounted for betwee 23% (lumpfish) and 88% (sole) of the total content of free amino compounds. In each species the regulatory volume decrease was associated with a reduction in the cellular content of taurine. Taurine contributed to between 6% (lumpfish) and 36% (flounder) of the cell shrinkage. There was a significant negative correlation, however, between the cellular concentration of taurine at normal osmolality and the capacity of the cells for regulatory volume decrease. Gamma-aminobutyric acid and/or glycine also contributed to the process of volume regulation, but to a lesser extent than taurine. The volume regulatory efflux of taurine and -aminobutyric acid were mediated by taurine channels. It is suggested that these channels also mediated the reduction in the cellular contents of glycine.Abbreviations cmp
counts per minute
- dw
dry weight
- GABA
-amino-n-butyric acid
- MW
molecular weight
- SD
standard deviation
- ww
wet weight 相似文献
70.
The effects of lead on Ca2+ homeostasis in nerve terminals was studied. Incubation with leadin vitro stimulated the activity of calmodulin and the maximum effect was observed at 30 M lead, higher concentrations had an inhibitory effect.In vivo exposure to lead increased the activity of calmodulin by 45%. Lead had an inhibitory effect on Ca2+ ATPase activity in both calmodulin-rich and calmodulin-depleted synaptic plasma membranes, the IC50 values for inhibition being 13.34 and 16.69 M respectively. Exogenous addition of calmodulin (5 g) and glutathione (1 mM) to calmodulin rich synaptic plasma membranes reversed the inhibition by IC50 concentration of lead.In vivo exposure of lead also significantly reduced the Ca2+ ATPase activity, resulting in an increase in intrasynaptosomal calcium. Concomitant with the increase in intrasynaptosomal calcium, lipid peroxidation values also increased significantly in lead-treated animals. In addition lead also had an inhibitory effect on depolarization induced Ca2+ uptake and the inhibition was found to be a competitive one. The results sugest that lead exerts its toxic effects by modifications of the intracellular calcium messenger system which would have serious consequences on neuronal functioning. 相似文献