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951.
Jia Qin Aleksey V. Zima Maura Porta Lothar A. Blatter Michael Fill 《Pflügers Archiv : European journal of physiology》2009,458(4):643-651
Trifluoperazine (TFP), a phenothiazine, is a commonly used antipsychotic drug whose therapeutic effects are attributed to
its central anti-adrenergic and anti-dopaminergic actions. However, TFP is also a calmodulin (CaM) antagonist and alters the
Ca2+ binding properties of calsequestrin (CSQ). The CaM and CSQ proteins are known modulators of sarcoplasmic reticulum (SR) Ca2+ release in ventricular myocytes. We explored TFP actions on cardiac SR Ca2+ release in cells and single type-2 ryanodine receptor (RyR2) channel activity in bilayers. In intact and permeabilized ventricular
myocytes, TFP produced an initial activation of RyR2-mediated SR Ca2+ release and over time depleted SR Ca2+ content. At the single channel level, TFP or nortryptiline (NRT; a tricyclic antidepressant also known to modify CSQ Ca2+ binding) increased the open probability (Po) of CSQ-free channels with an EC50 of 5.2 μM or 8.9 μM (respectively). This Po increase was due to elevated open event frequency at low drug concentrations
while longer mean open events sustained Po at higher drug concentrations. Activation of RyR2 by TFP occurred in the presence
or absence of CaM. TFP may also inhibit SR Ca uptake as well as increase RyR2 opening. Our results suggest TFP and NRT can
alter RyR2 function by interacting with the channel protein directly, independent of its actions on CSQ or CaM. This direct
action may contribute to the clinical adverse cardiac side effects associated with these drugs. 相似文献
952.
Large-conductance calcium-dependent potassium channels (BK channels) are homogeneously distributed along the somatodendritic
axis of layer 5 pyramidal neurons of the rat somatosensory cortex. The relevance of this conductance for dendritic calcium
electrogenesis was studied in acute brain slices using somatodendritic patch clamp recordings and calcium imaging. BK channel
activation reduces the occurrence of dendritic calcium spikes. This is reflected in an increased critical frequency of somatic
spikes necessary to activate the distal initiation zone. Whilst BK channels repolarise the somatic spike, they dampen it only
in the distal dendrite. Their activation reduces dendritic calcium influx via glutamate receptors. Furthermore, they prevent
dendritic calcium electrogenesis and subsequent somatic burst discharges. However, the time window for coincident somatic
action potential and dendritic input to elicit dendritic calcium events is not influenced by BK channels. Thus, BK channel
activation in layer 5 pyramidal neurons affects cellular excitability primarily by establishing a high threshold at the distal
action potential initiation zone.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
953.
Robert Stehle Johannes Solzin Bogdan Iorga Corrado Poggesi 《Pflügers Archiv : European journal of physiology》2009,458(2):337-357
Muscle contraction results from force-generating interactions between myosin cross-bridges on the thick filament and actin
on the thin filament. The force-generating interactions are regulated by Ca2+ via specialised proteins of the thin filament. It is controversial how the contractile and regulatory systems dynamically
interact to determine the time course of muscle contraction and relaxation. Whereas kinetics of Ca2+-induced thin-filament regulation is often investigated with isolated proteins, force kinetics is usually studied in muscle
fibres. The gap between studies on isolated proteins and structured fibres is now bridged by recent techniques that analyse
the chemical and mechanical kinetics of small components of a muscle fibre, subcellular myofibrils isolated from skeletal
and cardiac muscle. Formed of serially arranged repeating units called sarcomeres, myofibrils have a complete fully structured
ensemble of contractile and Ca2+ regulatory proteins. The small diameter of myofibrils (few micrometres) facilitates analysis of the kinetics of sarcomere
contraction and relaxation induced by rapid changes of [ATP] or [Ca2+]. Among the processes studied on myofibrils are: (1) the Ca2+-regulated switch on/off of the troponin complex, (2) the chemical steps in the cross-bridge adenosine triphosphatase cycle,
(3) the mechanics of force generation and (4) the length dynamics of individual sarcomeres. These studies give new insights
into the kinetics of thin-filament regulation and of cross-bridge turnover, how cross-bridges transform chemical energy into
mechanical work, and suggest that the cross-bridge ensembles of each half-sarcomere cooperate with each other across the half-sarcomere
borders. Additionally, we now have a better understanding of muscle relaxation and its impairment in certain muscle diseases. 相似文献
954.
Seventeen transient receptor potential (TRP) family proteins are encoded by the C. elegans genome, and they cover all of the seven TRP subfamilies, including TRPC, TRPV, TRPM, TRPN, TRPA, TRPP, and TRPML. Classical
forward and reverse genetic screens have isolated mutant alleles in every C. elegans trp gene, and their characterizations have revealed novel functions and regulatory mechanisms of TRP channels. For example, the
TRPC channels TRP-1 and TRP-2 control nicotine-dependent behavior, while TRP-3, a sperm TRPC channel, is regulated by sperm
activation and required for sperm–egg interactions during fertilization. Similar to their vertebrate counterparts, C. elegans TRPs function in sensory physiology. For instance, the TRPV channels OSM-9 and OCR-2 act in chemosensation, osmosensation,
and touch sensation, the TRPA member TRPA-1 regulates touch sensation, while the TRPN channel TRP-4 mediates proprioception.
Some C. elegans TRPM, TRPP, and TRPML members exhibit cellular functions similar to their vertebrate homologues and have provided insights
into human diseases, including polycystic kidney disease, hypomagnesemia, and mucolipidosis type IV. The availability of a
complete set of trp gene mutants in conjunction with its facile genetics makes C. elegans a powerful model for studying the function and regulation of TRP family channels in vivo. 相似文献
955.
Kwang-Hyun Park Young-Rae Lee Hyeon Hur Hong-Nu Yu So-Young Rah Uh-Hyun Kim Kang-Yeol Yu Chan-Moon Jin Myung-Kwan Han Jong-Suk Kim 《Microbial pathogenesis》2009
Endothelial hyperpermeability, a hallmark of septicemia, is induced by stress fiber formation, which is primarily regulated by the calcium/calmodulin signaling pathway in endothelial cells. We previously reported that trifluoperazine, a calcium/calmodulin antagonist, blocks Vibrio vulnificus cytolysin (VVC) -induced lethality at in vivo animal model. The object of this study was therefore to examine whether VVC induces stress fiber formation through calcium/calmodulin signaling in endothelial cells. Here, we monitored calcium-influx after treatment of VVC using confocal microscopy in CPAE cells, pulmonary endothelial cell line. Interestingly, we found that VVC-induced dose-dependently increases of [Ca2+]i in CPAE cells. Moreover, VVC-induced stress fiber formation as well as phosphorylation of myosin light chain (MLC) in a dose- and time-dependent manner, which was completely blocked by trifluoperazine. These results suggest that the calcium/calmodulin signaling pathway plays a pivotal role in VVC-induced hyperpermeability. 相似文献
956.
Background: Calcium ion is the first identified endogenous substance to function as both a first and second messenger via the stimulation of an extracellular calcium sensing receptor (CaR). CaR is a seven transmembrane G-protein-coupled receptor, which activates intracellular effectors, for example, it causes inositol phosphate (IP) accumulation to increase the release of intracellular calcium. Furthermore, more and more evidence shows that CaR is related to mediating the cellular functions in various cells. Recent findings: Since 2003, CaR has been detected to be functionally expressed in the atria and ventricle of the rat hearts. Recently, increasing evidence suggests that CaR has been involved in apoptosis in the ischemia/reperfusion heart through caspase-3-Cytochrome c and FasL/Fas and endoplasmic reticulum stress pathways and also involved in cardiac hypertrophy-induced by AngII through CaN pathway in neonatal rat cardiomyocytes. Summary: These results suggested that CaR in cardiac tissue might have a physiological and pathophysiological role in heart disease. This review revealed CaR's structure and function and emphasized the role of CaR in the cardiac tissues. 相似文献
957.
A novel Sr-containing calcium phosphate cement (CPC) with excellent compressive strength, good radiopacity and suitable setting time was developed in this work. The two-step hydration reaction resulted in a high compressive strength, with a maximum of up to 74.9 MPa. Sr was doped into the calcium-deficient hydroxyapatite as a hydrated product during the hydration reaction of the CPC. Because of the existence of Sr element and the compact microstructure after hydration, the Sr-containing CPC shows good radiopacity. It is expected to be used in orthopedic and maxillofacial surgery for bone defects repairing. 相似文献
958.
Marc Bohner Reto Luginbühl Christian Reber Nicola Doebelin Gamal Baroud Egle Conforto 《Acta biomaterialia》2009,5(9):3524-3535
A microsized α-tricalcium phosphate (α-TCP) powder was calcined at various temperatures (350 °C < T < 800 °C) for various durations (1–24 h) and the resulting physico-chemical and reactivity changes were measured. Without calcination, the α-TCP powder started reacting within minutes after contacting a 0.2 M Na2HPO4 solution as measured by isothermal calorimetry. The overall reaction was finished within a few days. After calcination at 350 °C T 550 °C for 24 h, no significant changes in the crystalline composition, crystallite size, particle size or specific surface area were noticed. However, the powder reactivity was progressively changed. More specifically, the hydraulic reaction of the powders calcined at 500 and 550 °C only started after 2–3 h whereas the overall hydraulic reaction was only slightly postponed, suggesting that physical or chemical changes had occurred at the particle surface. As mainly physical changes were detected at the particle surface during calcination at 500 °C, it was speculated that the appearance of this reaction delay (= induction time) was due to the disappearance of surface defects during the calcination step, i.e. to the need to create surface defects to induce dissolution and hence reaction. 相似文献
959.
Wei-Bor Tsai Rita Pei-Yeh Chen Kuang-Ling Wei Yi-Ru Chen Tai-Yan Liao Hsuan-Liang Liu Juin-Yih Lai 《Acta biomaterialia》2009,5(9):3467-3477
Layer-by-layer deposition of polyelectrolyte multilayer (PEM) thin films has recently been applied to biomaterial applications. This simple and versatile technique provides a wide variety of potential utilization by insertion of biomolecules such as cell adhesion peptides. In this work dual peptides containing RGD (a cell-binding domain) and LHRRVKI (a heparin-binding domain) were immobilized onto polystyrene by the PEM technique and the effects on osteoblast cell culture were investigated. These peptides were conjugated to the amino groups of poly(allylamine hydrochloride) and then adsorbed onto the top of a 10 layer poly(allylamine hydrochloride)/poly(acrylic acid) film assembled at either pH 2.0 or pH 6.5. Osteoblasts, isolated from neonatal rat calvariae, were then seeded and cultured on the peptide-conjugated surfaces. We found that the cells adhered and grew better on the RGD-conjugated PEM films. The osteoblasts exhibited a better differentiated phenotype on the pH 2.0 films than the pH 6.5 films with respect to calcium deposition. The incorporation of LHRRVKI did not support cell adhesion, growth and matrix mineral deposition. Our results showed that the efficacy of RGD conjugation on osteoblast behavior was affected by the base PEM film. 相似文献
960.
丹红注射液-磷酸钙骨水泥释放体系的力学性能、显微结构及体外释放 总被引:1,自引:0,他引:1
背景:研究证实磷酸钙骨水泥与药物混合后可能会影响磷酸钙骨水泥的固化反应过程和晶体形成过程,进而改变反应终产物的晶体结构和生物力学强度等性能。
目的:制备不同浓度丹红注射液-磷酸钙骨水泥释放体系,观察丹红注射液对磷酸钙骨水泥生物力学强度、晶体结构形态的影响以及复合释放体系体外释放的特点。
设计、时间及地点:对比观察实验,于2008-02在西安交通大学生物医学实验中心完成。
材料:制备0.5倍、1倍、2倍市售浓度的丹红注射液,并与磷酸钙骨水泥复合形成释放体系。
方法:载药磷酸钙骨水泥在模具中固化完全后,利用万能测试机检测其力学强度,扫描电镜观测晶体结构形态。以原儿茶醛为检测标志物,高效液相色谱法测定312 nm处物质浓度,以了解体外释放情况。
主要观察指标:①空白以及载药磷酸钙骨水泥微观结构的观察。②空白以及载药磷酸钙骨水泥生物力学强度的测定。③载药磷酸钙骨水泥体外释放药物浓度的测定。
结果:丹红注射液可使磷酸钙骨水泥力学强度下降,2倍浓度组最为显著(P < 0.05);丹红注射液与磷酸钙骨水泥复合未改变磷酸钙骨水泥微观晶体结构形态;释放体系在释放初期存在突释效应,约36 h后释放浓度趋于平稳。
结论:较大剂量丹红注射液与磷酸钙骨水泥复合可显著降低磷酸钙骨水泥力学强度;丹红注射液对磷酸钙骨水泥晶体结构形态无影响;磷酸钙骨水泥是丹红注射液较稳定的缓释载体。 相似文献