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31.
The effects of the sarcoplasmic reticulum (SR) Ca2+ pump inhibitor cyclopiazonic acid (CPA) were studied in saponin-permeabilized frog skeletal muscle fibres. Release of Ca2+ from the SR was triggered by brief (2 s) applications of 40 mM caffeine at 2-min intervals. Changes in [Ca2+] within the fibre were monitored continuously using Fura-2 fluorescence. At a bathing [Ca2+] of 100 nM, introduction of 20 μM CPA induced a slow release of Ca2+ from the SR. The following one to two caffeine-induced Ca2+ transients were markedly increased in amplitude and duration. Thereafter, the caffeine-induced Ca2+ transients decreased progressively and were barely detectable 6–7 min after introduction of CPA. However, increasing the
bathing [Ca2+] or increasing the Ca2+ loading period resulted in a partial recovery of the caffeine-induced Ca2+ transients, suggesting that pump inhibition is incomplete, even in the presence of 100 μM CPA. The slow Ca2+ efflux induced by CPA was insensitive to ryanodine, but absent following abolition of SR Ca2+ pump activity by ATP withdrawal. These results suggest that the caffeine-induced Ca2+ transient reflects a balance between efflux via the SR Ca2+ channel and reuptake by the Ca pump. Ca2+ release upon addition of CPA may result from inhibition of SR Ca2+ uptake, which reveals a tonic Ca2+ efflux that is independent of the Ca2+ release channels.
Received: 26 November 1997 / Received after revision: 12 January 1998 / Accepted: 13 January 1998 相似文献
32.
Aim: This study was conducted to investigate the mechanism of acidic pH‐induced contraction (APIC) with regard to Ca2+ handling using isometric tension recording experiments. Results: Decreasing extracellular pH from 7.4 to 6.5 produced a marked and sustained contraction of spontaneously hypertensive rat (SHR) aorta, that was 128.7 ± 2.0% of the 64.8 mm KCl‐induced contraction. Verapamil, an inhibitor of voltage‐dependent Ca2+ channels (VDCC) significantly inhibited the APIC. In Ca2+‐deficient solution, sustained contraction induced by acidic pH was abolished completely, while a transient contraction was still observed suggesting the release of Ca2+ from intracellular site. Ryanodine (1 μm ), a ryanodine receptor blocker, and 10 μm cyclopiazonic acid (CPA; a sarco/endoplasmic reticulum Ca2+ ATPase inhibitor) abolished the transient contraction induced by acidosis. In normal Ca2+‐containing solution, ryanodine significantly decreased the rate of rise as well as maximum level of APIC. Interestingly, ryanodine and CPA showed an additive inhibitory effect with verapamil and the combined treatment of ryanodine or CPA with verapamil nearly abolished the APIC. Conclusions: It is concluded that acidic pH induces Ca2+ release from ryanodine/CPA‐sensitive store of sarcoplasmic reticulum in SHR aorta. This Ca2+ plays an important role in the facilitation of the rate of rise of APIC, as well as contributing to the sustained contraction via a mechanism which is independent of Ca2+ influx through VDCC. 相似文献
33.
Annunziata Gloghini Antonino Carbone 《Virchows Archiv : an international journal of pathology》1990,416(3):197-204
Summary We performed a comparative immunohisto-cytochemical study of the distribution patterns of laminin and follicular dendritic reticulum cells (DRCs) within their follicular microenvironment in both nodular or diffuse B-cell non Hodgkin's lymphomas (NHLs). Twenty nine cases of immunophenotypically diagnosed B-cell NHLs (19 of follicular center cell origin-FCCL- and 10 of the diffuse well differentiated lymphocytic type-WDLL-) and five reactive lymph nodes with follicular hyperplasia were analyzed by immunoperoxidase and immunofluorescence techniques. Serial frozen sections and cytospin preparations were tested either with single antibodies anti laminin and DRC-1, or paired reagents in double labeling immunofluorescence. Our results indicated consistently that within both the reactive germinal centers and the neoplastic nodules of FCCL laminin immunostaining visualized a punctate-granular pattern apart from the linear vascular basement membrane positivity. Double immunofluorescence assay demonstrated that there was a close parallelism between this laminin staining pattern and DRC-1 distribution showing a well developed DRCs meshwork; in the diffuse tumour areas of both FCCL and WDLL, laminin immunoreactivity was found only in those cases in which nests of DRCs were observed. Double immunofluorescence studies performed on cytospin preparations demonstrated that the groups of cells containing DRC-1 positive cells, contained a positivity for laminin, although within the cell the staining for DRC-1 was intense and diffuse, while that for laminin was granular and more sparse. Our results suggested that these laminin and DRC-1 positive reactive sites may be present on the same cells. Since the reduction in number or loss of both DRCs and their related immunostaining for laminin within the microenvironment was consistently associated with a loss of nodularity by lymphoma cells, whereas nodularity in reactive and neoplastic conditions was associated with a rich DRCs meshwork and the related laminin immunostaining, a trapping function of DRCs exercised in the presence of laminin should be considered.This work was supported in part by a Grant N 87.02799.44 from the Consiglio Nazionale delle Ricerche, Progetto Finalizzato Oncologia, Rome, and by the Associazione Italiana per la Ricerca sul Cancro, Milan, Italy 相似文献
34.
The shal gene encoding the transient potassium current, I
A, plays important roles in shaping the firing properties of neurons in the pyloric network in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. However, when we overexpressed the shal protein in pyloric dilator (PD) neurons, the effect of increased I
A was compensated by a parallel upregulation of the hyperpolarization activated inward current (I
h). In an attempt to temporally separate the overexpression of shal from the compensatory up-regulation of I
h channels, we inserted an endoplasmic reticulum (ER) export signal sequence, FCYENE, into the shal gene. This signal sequence accelerated the surface expression of shal protein in Xenopus oocytes and PD neurons. However, the accelerated expression of shal still did not alter the firing properties of the injected neuron, suggesting that the compensatory upregulation of I
h occurs simultaneously with the upregulation of I
A. 相似文献
35.
The sarcoplasmic reticulum (SR) plays the central role in regulating the free myoplasmic Ca2+ level for the contractile activation of skeletal muscle. The initial stages of the voltage-controlled Ca2+ release mechanism are known in molecular detail. However, there is still very little known about the later stages of Ca2+ uptake and total Ca2+ turnover in the contraction–relaxation cycle under normal physiological conditions or under conditions influenced by fatigue or disease. Ca2+ uptake and release are both accompanied by ‘counter-ion’ movements across the SR membrane which prevent or reduce the generation of SR membrane potentials and balance for electroneutrality in the SR lumen. The SR membrane is permeable for the cations K+, Na+, H+ and Mg2+ and the anion Cl-. Using electron-probe X-ray microanalysis, it has been shown that during tetanic stimulation the Ca2+ release was mainly balanced by uptake of K+ and Mg2+, leaving a charge deficit that was assumed to be neutralized via H+ ion or organic counter-ion movement. The low time resolution of electron-probe X-ray microanalysis leaves the possibility of other transient concentration changes in the SR, e.g. for Cl- ions. Possible physiological roles of the SR counter-ion conductances can be tested using skinned muscle fibre preparations with intact sarcoplasmic reticulum and removed or chemically permeabilized outer sarcolemma. In skinned fibres, the SR K+ conductance can be effectively reduced with SR K+ channel blockers such as 4-aminopyridine, tetraethylammonium and decamethonium. Interestingly, these blockers increase Ca2+ loading as well as Ca2+ release, whereas other less specific blockers, such as 1.10-bis-quanidino-n-decane, seem to reduce Ca2+ release, possibly also via blocking Ca2+ release channels. Thus, it seems very important also to test the effects of counter-currents carried by K+, Mg2+, H+ or Cl- ions on intact and voltage-clamped single-fibre preparations. 相似文献
36.
L.P. RUCO A.J.H. GEARING R. PIGOTT D. POMPONI V.L. BURGIO A. CAFOLLA A. BAIOCCHINI C.D. BARONI 《Histopathology》1991,19(6):523-528
The inducible adhesion molecules mediate important functions in the lymphoid tissues. We have investigated the expression of intercellular adhesion molecule 1 (ICAM-1), endothelial leucocyte adhesion molecule 1 (ELAM-1), vascular cell adhesion molecule 1 (VCAM-1), and platelet endothelial cell adhesion molecule (PECAM/CD31), using immunocytochemistry on cryostat sections of five lymph nodes from patients with Castleman's disease of the hyaline-vascular type. All five cases were characterized by marked hyperplasia of follicular dendritic reticulum cells, which were extensively present even in the mantle zone. Hyperplastic follicular dendritic reticulum cells showed marked expression of VCAM-1, and weak expression of ICAM-1. In two cases, several dysplastic giant cells with aberrant, polyploid nuclei showed aberrant expression of ELAM-1, an endothelium-restricted molecule. Dysplastic giant cells were positive with DRC-1 (an antibody to dendritic reticulum cells), VCAM-1 and occasionally ICAM-1, were negative for the endothelial cell markers factor VIII-related antigen and CD31 and were non-proliferating (Kl-67-). Cells positive for ICAM-1 or VCAM-1 were rare in the interfollicular areas. In all cases vascular hyperplasia was prominent, but endothelial cells were poorly activated in terms of expression of inducible adhesion molecules and of HLA-DR antigens. The possibility that dysplastic follicular dendritic reticulum cells have a pathogenetic role in Castleman's disease is discussed. 相似文献
37.
Yukichi Tanaka 《Virchows Archiv : an international journal of pathology》1987,410(2):125-132
Summary The present study concerns the immunocytochemical localization of S-100 protein and subunits in the cells of human lymphoreticular tissue and their related tumours. The subunit is mainly localized in dendritic cells, most likely the dendritic reticulum cells (DRCs) located within the germinal centers, while the subunit is mainly localized in the interdigitating reticulum cells (IRCs) in the paracortical area and in Histiocytosis X cells. No immunoreactivity for either subunit was found in the majority of normal lymphocytes, macrophages, malignant lymphoma cells, or xanthoma cells.The DRCs and IRCs are generally considered to show different distribution in the lymphoid tissues and demonstrate some difference in their immunocytochemical and enzyme-histochemical features. It is suggested that S-100 subunits can be used as useful markers for these two types of dendritic cells and investigation of these subunits may provide more information for the study of human lymphoreticular system. 相似文献
38.
ER chaperone functions during normal and stress conditions 总被引:8,自引:0,他引:8
39.
Damage of purkinje cell axons following chronic phenytoin administration: An animal model of distal axonopathy 总被引:3,自引:0,他引:3
Summary An animal model of central distal axonopathy following chronic administration of phenytoin is described. Male C57/BL6J mice received diphenylhydantoin (DPH) in the daily diet (liquid diet Stardit, supplemented with vitamins) over a period of 8 weeks. Control and experimental animals were pair-fed.Twelve mice of both groups were perfused via the left ventricle with glutaraldehyde. Representative samples of the cerebral cortex (area 3), cerebellum (vermis and deep cerebellar nuclei), thalamus, hypothalamus, and liver were embedded in araldite. Semithin sections and electron microscopy of the cerebellar vermis revealed marked dystrophic changes in the Purkinje cell axons. The presynaptic segments of Purkinje cell axons in the deep cerebellar nuclei showed massive enlargement and swelling due to accumulation of spherical particles and tubular structures in the axoplasm. These structures represent a proliferation of the smooth endoplasmic reticulum.Identical changes were found in hepatocytes of treated animals. Because phenytoin induces hepatic microsomal enzymes, we suggest that phenytoin-related Purkinje cell damage may be produced by an induction of Purkinje cell microsomes with proliferation of the smooth endoplasmic reticulum which causes a swelling and enlargement of presynaptic segments of Purkinje cell axons in deep cerebellar nuclei. Chronic phenytoin administration to mice is a new model of phenytoin-induced encephalopathy and of distal axonopathy of cerebellar neurons.Supported by the Deutsche ForschungsgemeinschaftPresented in Part at the Joint Meeting of the German and Scandinavian Neuropathologists, Turku, Finland, June 3–4, 1983 相似文献
40.
Summary The mechanism of quinidine action on rabbit cardiac and skeletal muscle was examined with functionally skinned muscle-fiber preparations. By using these preparations we could correlate measurements of muscle tension with the effect of quinidine on the Ca2+ activation of the contractile proteins and on the Ca2+ uptake and release from the sarcoplasmic reticulum (SR).
Effect of quinidine on the contractile proteins. Quinidine concentrations above 0.5 mmol/l increased the maximal Ca2+-activated tension development 12% for papillary muscle and 5% for soleus (slow-twitch). Adductor magnus (fast-twitch) showed no significant change. Quinidine (0.1–1.0 mmol/l) also increased the submaximal Ca2+-activated tension development for the three muscle types (papillary muscle=soleus>adductor magnus) and shifted the [Ca2+]-tension curves to the left in a dose-dependent fashion.
Effects of quinidine on the Ca
2+ uptake and release from the SR. Sarcoplasmic reticulum of skinned fibers was loaded with Ca2+ (uptake phase), then Ca2+ was released by 25 mmol/l caffeine (release phase) giving a tension transient. The area under the tension transient was used to estimate the amount of Ca2+ released. Quinidine (>0.5 mmol/l) decreased the Ca2+ uptake (soleus>adductor magnus>papillary muscle) and increased the Ca2+ release [papillary muscle=soleus adductor magnus (only at 1.5 mmol/l, the highest concentration tested)] from the SR of all three muscles in a dose-dependent manner. Quinidine at low concentration (0.1 and 0.5 mmol/l) increased the caffeine-induced tension transient of papillary muscle and higher quinidine concentrations (1.0 and 1.5 mmol/l) decreased the caffeine-induced tension transient of soleus and adductor magnus during both the uptake and release phases. The decreased Ca2+ uptake of papillary muscle in 1.5 mmol/l quinidine was antagonized by increasing the free Mg2+ from 0.032 to 0.32 mmol/l.In summary, quinidine has similar mechanisms of action in all three muscles: increased Ca2+ activation of the contractile proteins, decreased Ca2+ uptake and increased Ca2+ release from the SR in functionally skinned muscle fibers. We conclude that quinidine-induced decreases in Ca2+ uptake by the SR could be responsible for quinidine-induced myocardial depression and that quinidine-induced increases in Ca2+ activation of the contractile proteins and Ca2+ release from the SR could be responsible for the increases in skeletal muscle contraction caused by quinidine. 相似文献